TY - JOUR AU - Hegyi, Bence AU - Horváth, Balázs AU - Váczi, Krisztina AU - Gönczi, Mónika AU - Kistamás, Kornél AU - Ruzsnavszky, Ferenc AU - Veress, Roland AU - Izu, Leighton T. AU - Chen-Izu, Ye AU - Bányász, Tamás AU - Magyar, János AU - Csernoch, László AU - Nánási, Péter Pál AU - Szentandrássy, Norbert TI - Ca2+-activated Cl- current is antiarrhythmic by reducing both spatial and temporal heterogeneity of cardiac repolarization. JF - JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY J2 - J MOL CELL CARDIOL VL - 109 PY - 2017 SP - 27 EP - 37 PG - 11 SN - 0022-2828 DO - 10.1016/j.yjmcc.2017.06.014 UR - https://m2.mtmt.hu/api/publication/3278587 ID - 3278587 N1 - Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Department of Pharmacology, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 3503, Davis, CA 95616, United States Faculty of Pharmacy, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary MTA-DE Momentum, Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Department of Biomedical Engineering, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 2303, Davis, CA 95616, United States Department of Internal Medicine, Division of Cardiology, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 6315, Davis, CA 95616, United States Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Export Date: 8 September 2021 CODEN: JMCDA Correspondence Address: Nánási, P.P.; Department of Physiology, Nagyerdei krt 98, P.O. Box 22, Hungary; email: nanasi.peter@med.unideb.hu Funding details: National Heart, Lung, and Blood Institute, NHLBI, R01HL090880, R01HL123526 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: The authors thank Miss ?va S?gi for her excellent technical assistance. The support of the Momentum program (LP2012-41) of the Hungarian Academy of Sciences is gratefully acknowledged. AB - The role of Ca2+-activated Cl- current (ICl(Ca)) in cardiac arrhythmias is still controversial. It can generate delayed afterdepolarizations in Ca2+-overloaded cells while in other studies incidence of early afterdepolarization (EAD) was reduced by ICl(Ca). Therefore our goal was to examine the role of ICl(Ca) in spatial and temporal heterogeneity of cardiac repolarization and EAD formation. Experiments were performed on isolated canine cardiomyocytes originating from various regions of the left ventricle; subepicardial, midmyocardial and subendocardial cells, as well as apical and basal cells of the midmyocardium. ICl(Ca) was blocked by 0.5mmol/L 9-anthracene carboxylic acid (9-AC). Action potential (AP) changes were tested with sharp microelectrode recording. Whole-cell 9-AC-sensitive current was measured with either square pulse voltage-clamp or AP voltage-clamp (APVC). Protein expression of TMEM16A and Bestrophin-3, ion channel proteins mediating ICl(Ca), was detected by Western blot. 9-AC reduced phase-1 repolarization in every tested cell. 9-AC also increased AP duration in a reverse rate-dependent manner in all cell types except for subepicardial cells. Neither ICl(Ca) density recorded with square pulses nor the normalized expressions of TMEM16A and Bestrophin-3 proteins differed significantly among the examined groups of cells. The early outward component of ICl(Ca) was significantly larger in subepicardial than in subendocardial cells in APVC setting. Applying a typical subepicardial AP as a command pulse resulted in a significantly larger early outward component in both subepicardial and subendocardial cells, compared to experiments when a typical subendocardial AP was applied. Inhibiting ICl(Ca) by 9-AC generated EADs at low stimulation rates and their incidence increased upon beta-adrenergic stimulation. 9-AC increased the short-term variability of repolarization also. We suggest a protective role for ICl(Ca) against risk of arrhythmias by reducing spatial and temporal heterogeneity of cardiac repolarization and EAD formation. LA - English DB - MTMT ER - TY - JOUR AU - Orosz, Andrea AU - Baczkó, István AU - Nyiraty, Szabolcs AU - Körei, Anna Erzsébet AU - Putz, Zsuzsanna AU - Takács, Róbert AU - Nemes, Attila AU - Várkonyi, Tamás AU - Balogh, László AU - Ábrahám, György AU - Kempler, Péter AU - Papp, Gyula AU - Varró, András AU - Lengyel, Csaba Attila TI - Increased Short-Term Beat-to-Beat QT Interval Variability in Patients with Impaired Glucose Tolerance JF - FRONTIERS IN ENDOCRINOLOGY J2 - FRONT ENDOCRINOL VL - 8 PY - 2017 PG - 8 SN - 1664-2392 DO - 10.3389/fendo.2017.00129 UR - https://m2.mtmt.hu/api/publication/3245238 ID - 3245238 N1 - Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary First Department of Medicine, University of Szeged, Szeged, Hungary First Department of Medicine, Semmelweis University, Budapest, Hungary Second Department of Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary Juhász Gyula Faculty of Education, Institute of Physical Education and Sport Science, University of Szeged, Szeged, Hungary MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary Cited By :12 Export Date: 16 April 2021 Correspondence Address: Lengyel, C.; Department of Pharmacology and Pharmacotherapy, Hungary; email: lecs.in1st@gmail.com Chemicals/CAS: glucose, 50-99-7, 84778-64-3; hemoglobin A1c, 62572-11-6; octreotide, 83150-76-9, 1607842-55-6 Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary First Department of Medicine, University of Szeged, Szeged, Hungary First Department of Medicine, Semmelweis University, Budapest, Hungary Second Department of Medicine and Cardiology Centre, University of Szeged, Szeged, Hungary Juhász Gyula Faculty of Education, Institute of Physical Education and Sport Science, University of Szeged, Szeged, Hungary MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary Cited By :12 Export Date: 17 May 2021 Correspondence Address: Lengyel, C.; Department of Pharmacology and Pharmacotherapy, Hungary; email: lecs.in1st@gmail.com Chemicals/CAS: glucose, 50-99-7, 84778-64-3; hemoglobin A1c, 62572-11-6; octreotide, 83150-76-9, 1607842-55-6 AB - Prediabetic states and diabetes are important risk factors for cardiovascular morbidity and mortality. Determination of short-term QT interval variability (STVQT) is a non-invasive method for assessment of proarrhythmic risk. The aim of the study was to evaluate the STVQT in patients with impaired glucose tolerance (IGT). 18 IGT patients [age: 63 +/- 11 years, body mass index (BMI): 31 +/- 6 kg/m2, fasting glucose: 6.0 +/- 0.4 mmol/l, 120 min postload glucose: 9.0 +/- 1.0 mmol/l, hemoglobin A1c (HbA1c): 5.9 +/- 0.4%; mean +/- SD] and 18 healthy controls (age: 56 +/- 9 years, BMI: 27 +/- 5 kg/m2, fasting glucose: 5.2 +/- 0.4 mmol/l, 120 min postload glucose: 5.5 +/- 1.3 mmol/l, HbA1c: 5.4 +/- 0.3%) were enrolled into the study. ECGs were recorded, processed, and analyzed off-line. The RR and QT intervals were expressed as the average of 30 consecutive beats, the temporal instability of beat-to-beat repolarization was characterized by calculating STVQT as follows: STVQT = Sigma|QTn + 1 - QTn| (30x radical2)-1. Autonomic function was assessed by means of standard cardiovascular reflex tests. There were no differences between IGT and control groups in QT (411 +/- 43 vs 402 +/- 39 ms) and QTc (431 +/- 25 vs 424 +/- 19 ms) intervals or QT dispersion (44 +/- 13 vs 42 +/- 17 ms). However, STVQT was significantly higher in IGT patients (5.0 +/- 0.7 vs 3.7 +/- 0.7, P < 0.0001). The elevated temporal STVQT in patients with IGT may be an early indicator of increased instability of cardiac repolarization during prediabetic conditions. LA - English DB - MTMT ER - TY - JOUR AU - Horváth, Balázs AU - Váczi, Krisztina AU - Hegyi, Bence AU - Gönczi, Mónika AU - Dienes, Beatrix AU - Kistamás, Kornél AU - Bányász, Tamás AU - Magyar, János AU - Baczkó, István AU - Varró, András AU - Seprényi, György AU - Csernoch, László AU - Nánási, Péter Pál AU - Szentandrássy, Norbert TI - Sarcolemmal Ca2+-entry through L-type Ca2+ channels controls the profile of Ca2+-activated Cl- current in canine ventricular myocytes. JF - JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY J2 - J MOL CELL CARDIOL VL - 97 PY - 2016 SP - 125 EP - 139 PG - 15 SN - 0022-2828 DO - 10.1016/j.yjmcc.2016.05.006 UR - https://m2.mtmt.hu/api/publication/3066993 ID - 3066993 N1 - Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Faculty of Pharmacy, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary MTA-DE Momentum, Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Dóm tér 12, P.O. Box 427, Szeged, H-6720, Hungary MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Dóm tér 12, P.O. Box 427, Szeged, H-6720, Hungary Department of Medical Biology, Faculty of Medicine, University of Szeged, Somogyi Béla utca 4, P.O. Box 427, Szeged, H-6720, Hungary Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary Cited By :9 Export Date: 30 September 2019 CODEN: JMCDA Correspondence Address: Szentandrássy, N.; Department of Physiology, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Hungary; email: szentandrassy.norbert@med.unideb.hu Chemicals/CAS: calcium ion, 14127-61-8; Biomarkers; Calcium Channel Blockers; Calcium Channels, L-Type; Chloride Channels AB - Ca2+-activated Cl- current (ICl(Ca)) mediated by TMEM16A and/or Bestrophin-3 may contribute to cardiac arrhythmias. The true profile of ICl(Ca) during an actual ventricular action potential (AP), however, is poorly understood. We aimed to study the profile of ICl(Ca) systematically under physiological conditions (normal Ca2+ cycling and AP voltage-clamp) as well as in conditions designed to change [Ca2+]i. The expression of TMEM16A and/or Bestrophin-3 in canine and human left ventricular myocytes was examined. The possible spatial distribution of these proteins and their co-localization with Cav1.2 was also studied. The profile of ICl(Ca), identified as a 9-anthracene carboxylic acid-sensitive current under AP voltage-clamp conditions, contained an early fast outward and a late inward component, overlapping early and terminal repolarizations, respectively. Both components were moderately reduced by ryanodine, while fully abolished by BAPTA, but not EGTA. [Ca2+]i was monitored using Fura-2-AM. Setting [Ca2+]i to the systolic level measured in the bulk cytoplasm (1.1muM) decreased ICl(Ca), while application of Bay K8644, isoproterenol, and faster stimulation rates increased the amplitude of ICl(Ca). Ca2+-entry through L-type Ca2+ channels was essential for activation of ICl(Ca). TMEM16A and Bestrophin-3 showed strong co-localization with one another and also with Cav1.2 channels, when assessed using immunolabeling and confocal microscopy in both canine myocytes and human ventricular myocardium. Activation of ICl(Ca) in canine ventricular cells requires Ca2+-entry through neighboring L-type Ca2+ channels and is only augmented by SR Ca2+-release. Substantial activation of ICl(Ca) requires high Ca2+ in the dyadic clefts which can be effectively buffered by BAPTA, but not EGTA. LA - English DB - MTMT ER - TY - JOUR AU - Horváth, Balázs AU - Hegyi, Bence AU - Kistamás, Kornél AU - Váczi, Krisztina AU - Bányász, Tamás AU - Magyar, János AU - Szentandrássy, Norbert AU - Nánási, Péter Pál TI - Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes JF - CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - CAN J PHYSIOL PHARM VL - 93 PY - 2015 IS - 7 SP - 527 EP - 534 PG - 8 SN - 0008-4212 DO - 10.1139/cjpp-2014-0511 UR - https://m2.mtmt.hu/api/publication/2836489 ID - 2836489 N1 - Megjegyzés-24983292, 24928582, 24928596, 24928599, 24928725, 24974820, 24927946 PN 1 AB - The present study was designed to investigate the influence of cytosolic Ca2+concentration ([Ca2+]i) on action potential duration (APD) and on the incidence of earlyafterdepolarizations (EADs) in canine ventricular cardiomyocytes. Action potentials (AP)of isolated cells were recorded using conventional sharp microelectrodes and concomitant[Ca2+]i was monitored by the fluorescent dye, Fura-2. EADs were evoked at 0.2 Hz pacingrate by inhibiting the rapid delayed rectifier K+ current with dofetilide, by activating thelate sodium current with veratridine, or by activating the L-type calcium current with BAYK8644. These interventions progressively prolonged the AP and resulted in initiation ofEADs. Reducing [Ca2+]i by application of the cell-permeant Ca2+ chelator BAPTA-AMlengthened the AP at 1 Hz if it was applied alone or in the presence of veratridine and BAYK8644. BAPTA-AM, however, shortened the AP after pretreating the cells with dofetilide.The incidence of the evoked EADs was decreased by BAPTA-AM strongly in dofetilideand moderately in veratridine, while it was increased by BAPTA-AM in the presence ofBAY K8644. Based on these experimental data changes in [Ca2+]i have marked effects onAPD as well as on EAD incidence, however, the underlying mechanisms may be differentdepending on the mechanism of EAD generation. LA - English DB - MTMT ER - TY - JOUR AU - Kistamás, Kornél AU - Szentandrássy, Norbert AU - Hegyi, Bence AU - Váczi, Krisztina AU - Ruzsnavszky, Ferenc AU - Horváth, Balázs AU - Bányász, Tamás AU - Nánási, Péter Pál AU - Magyar, János TI - Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes JF - JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - J PHYSIOL PHARMACOL VL - 66 PY - 2015 IS - 1 SP - 73 EP - 81 PG - 9 SN - 0867-5910 UR - https://m2.mtmt.hu/api/publication/2836490 ID - 2836490 AB - The aim of the present work was to study the influence of changes in intracellular calcium concentration ([Ca2+]i) onbeat-to-beat variability (short term variability, SV) of action potential duration (APD) in isolated canine ventricularcardiomyocytes. Series of action potentials were recorded from enzymatically isolated canine ventricular cells usingconventional microelectrode technique. Drug effects on SV were evaluated as relative SV changes determined byplotting the drug-induced changes in SV against corresponding changes in APD and comparing these data to theexponential SV-APD function obtained with inward and outward current injections. Exposure of myocytes to the Ca2+chelator BAPTA-AM (5 ?M) decreased, while Ca2+ ionophore A23187 (1 ?M) increased the magnitude of relative SV.Both effects were primarily due to the concomitant changes in APD. Relative SV was reduced by BAPTA-AM undervarious experimental conditions including pretreatment with veratridine, BAY K8644, dofetilide or E-4031.Contribution of transient changes of [Ca2+]i due to Ca2+ released from the sarcoplasmic reticulum (SR) was studied using10 ?M ryanodine and 1 ?M cyclopiazonic acid: relative SV was reduced by both agents. Inhibition of the Na+-Ca2+exchanger by 1 ?M SEA0400 increased relative SV.It is concluded that elevation of [Ca2+]i increases relative SVsignificantly. More importantly, Ca2+ released from the SR is an important component of this effect. LA - English DB - MTMT ER - TY - JOUR AU - Szentandrássy, Norbert AU - Kistamás, Kornél AU - Hegyi, Bence AU - Horváth, Balázs AU - Ruzsnavszky, Ferenc AU - Váczi, Krisztina AU - Magyar, János AU - Bányász, Tamás AU - Varró, András AU - Nánási, Péter Pál TI - Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 467 PY - 2015 IS - 7 SP - 1431 EP - 1443 PG - 13 SN - 0031-6768 DO - 10.1007/s00424-014-1581-4 UR - https://m2.mtmt.hu/api/publication/2763937 ID - 2763937 N1 - Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :16 Export Date: 26 September 2019 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :16 Export Date: 30 September 2019 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :16 Export Date: 3 October 2019 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :16 Export Date: 4 October 2019 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :18 Export Date: 27 January 2020 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :18 Export Date: 13 February 2020 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :19 Export Date: 14 February 2020 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :27 Export Date: 16 April 2021 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :29 Export Date: 17 May 2021 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 Department of Physiology, University of Debrecen, 4012, Nagyerdei krt 98, Debrecen, Hungary Department of Dental Physiology and Pharmacology, University of Debrecen, Debrecen, Hungary Division of Sport Physiology, Department of Physiology, University of Debrecen, Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Cited By :29 Export Date: 31 May 2021 CODEN: PFLAB Correspondence Address: Nánási, P.P.; Department of Physiology, 4012, Nagyerdei krt 98, Hungary Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; calcium, 7440-70-2, 14092-94-5; dofetilide, 115256-11-6; isoprenaline, 299-95-6, 51-30-9, 6700-39-6, 7683-59-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nisoldipine, 63675-72-9; tetrodotoxin, 4368-28-9, 4664-41-9; veratridine, 71-62-5; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Calcium; Cardiotonic Agents; Chromans; dofetilide; HMR 1556; Ion Channels; Isoproterenol; Lidocaine; Nisoldipine; Phenethylamines; Potassium Channel Blockers; Sulfonamides; Tetrodotoxin; Veratridine Tradenames: bay k 8644; hmr 1556 AB - Although beat-to-beat variability (short-term variability, SV) of action potential duration (APD) is considered as a predictor of imminent cardiac arrhythmias, the underlying mechanisms are still not clear. In the present study, therefore, we aimed to determine the role of the major cardiac ion currents, APD, stimulation frequency, and changes in the intracellular Ca2+ concentration ([Ca2+]i) on the magnitude of SV. Action potentials were recorded from isolated canine ventricular cardiomyocytes using conventional microelectrode techniques. SV was an exponential function of APD, when APD was modified by current injections. Drug effects were characterized as relative SV changes by comparing the drug-induced changes in SV to those in APD according to the exponential function obtained with current pulses. Relative SV was increased by dofetilide, HMR 1556, nisoldipine, and veratridine, while it was reduced by BAY K8644, tetrodotoxin, lidocaine, and isoproterenol. Relative SV was also increased by increasing the stimulation frequency and [Ca2+]i. In summary, relative SV is decreased by ion currents involved in the negative feedback regulation of APD (I Ca, I Ks, and I Kr), while it is increased by I Na and I to. We conclude that drug-induced effects on SV should be evaluated in relation with the concomitant changes in APD. Since relative SV was decreased by ion currents playing critical role in the negative feedback regulation of APD, blockade of these currents, or the beta-adrenergic pathway, may carry also some additional proarrhythmic risk in addition to their well-known antiarrhythmic action. LA - English DB - MTMT ER - TY - JOUR AU - Váczi, Krisztina AU - Hegyi, Bence AU - Ruzsnavszky, Ferenc AU - Kistamás, Kornél AU - Horváth, Balázs AU - Bányász, Tamás AU - Nánási, Péter Pál AU - Szentandrássy, Norbert AU - Magyar, János TI - 9-Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential. JF - NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY J2 - N-S ARCH PHARMACOL VL - 388 PY - 2015 IS - 1 SP - 87 EP - 100 PG - 14 SN - 0028-1298 DO - 10.1007/s00210-014-1050-9 UR - https://m2.mtmt.hu/api/publication/2805750 ID - 2805750 AB - Understanding the role of ionic currents in shaping the cardiac action potential (AP) has great importance as channel malfunctions can lead to sudden cardiac death by inducing arrhythmias. Therefore, researchers frequently use inhibitors to selectively block a certain ion channel like 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 9-anthracene carboxylic acid (9-AC) for calcium-activated chloride current (ICl(Ca)). This study aims to explore which blocker is preferable to study ICl(Ca). Whole-cell voltage-clamp technique was used to record ICa,L, IKs, IKr and IK1, while action potentials were measured using sharp microelectrodes. DIDS- (0.2 mM) and 9-AC-sensitive (0.5 mM) currents were identical in voltage-clamp conditions, regardless of intracellular Ca(2+) buffering. DIDS-sensitive current amplitude was larger with the increase of stimulation rate and correlated well with the rate-induced increase of calcium transients. Both drugs increased action potential duration (APD) to the same extent, but the elevation of the plateau potential was more pronounced with 9-AC at fast stimulation rates. On the contrary, 9-AC did not influence either the AP amplitude or the maximal rate of depolarization (V max), but DIDS caused marked reduction of V max. Both inhibitors reduced the magnitude of phase-1, but, at slow stimulation rates, this effect of DIDS was larger. All of these actions on APs were reversible upon washout of the drugs. Increasing concentrations of 9-AC between 0.1 and 0.5 mM in a cumulative manner gradually reduced phase-1 and increased APD. 9-AC at 1 mM had no additional actions upon perfusion after 0.5 mM. The half-effective concentration of 9-AC was approximately 160 muM with a Hill coefficient of 2. The amplitudes of ICa,L, IKs, IKr and IK1 were not changed by 0.5 mM 9-AC. These results suggest that DIDS is equally useful to study ICl(Ca) during voltage-clamp but 9-AC is superior in AP measurements for studying the physiological role of ICl(Ca) due to the lack of sodium channel inhibition. 9-AC has also no action on other ion currents (ICa,L, IKr, IKs, IK1); however, ICa,L tracings can be contaminated with ICl(Ca) when measured in voltage-clamp condition. LA - English DB - MTMT ER - TY - JOUR AU - Szentandrássy, Norbert AU - Papp, Ferenc AU - Hegyi, Bence AU - Bartók, Ádám AU - Krasznai, Zoltán AU - Nánási, Péter Pál TI - Tetrodotoxin blocks native cardiac L-type calcium channels but not CaV1.2 channels expressed in HEK cells. JF - JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - J PHYSIOL PHARMACOL VL - 64 PY - 2013 IS - 6 SP - 807 EP - 810 PG - 4 SN - 0867-5910 UR - https://m2.mtmt.hu/api/publication/2502508 ID - 2502508 N1 - Összes idézések száma a WoS-ban: 0 AB - Tetrodotoxin (TTX) has been believed for a long time to be a selective inhibitor of voltage-gated fast Na(+) channels in excitable tissues, including mammalian myocardium. Recently TTX has been shown to block cardiac L-type Ca(2+) current (ICa,L). Furthermore, this inhibition was ascribed to binding of TTX to the outer pore of the Ca(2+) channel, contributing to the selectivity filter region. In this study the TTX-sensitivity of Cav1.2 channels, expressed in HEK cells, was tested using the whole cell version of the patch clamp technique and compared to the TTX-sensitivity of native canine ICa,L. Cav1.2 channels mediate Ca(2+) current in ventricular myocardium of various mammalian species. Surprisingly, TTX failed to inhibit Cav1.2 current up to the concentration of 100 muM - in contrast to ICa,L - in spite of the fact that the kinetic properties of the ICa,L and Cav1.2 currents were similar. The possible reasons for this discrepancy are discussed. Present results may question the suitability of a single pore-forming channel subunit, expressed in a transfection system, for electrophysiological or pharmacological studies. LA - English DB - MTMT ER - TY - JOUR AU - Bányász, Tamás AU - Horváth, Balázs AU - Jian, Z AU - Izu, LT AU - Chen-Izu, Y TI - Sequential dissection of multiple ionic currents in single cardiac myocytes under action potential-clamp JF - JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY J2 - J MOL CELL CARDIOL VL - 50 PY - 2011 IS - 3 SP - 578 EP - 581 PG - 4 SN - 0022-2828 DO - 10.1016/j.yjmcc.2010.12.020 UR - https://m2.mtmt.hu/api/publication/1981464 ID - 1981464 LA - English DB - MTMT ER - TY - JOUR AU - Pueyo, E AU - Corrias, A AU - Virág, László AU - Jost, Norbert László AU - Szél, Tamás AU - Varró, András AU - Szentandrássy, Norbert AU - Nánási, Péter Pál AU - Burrage, K AU - Rodriguez, B TI - A multiscale investigation of repolarization variability and its role in cardiac arrhythmogenesis JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 101 PY - 2011 IS - 12 SP - 2892 EP - 2902 PG - 11 SN - 0006-3495 DO - 10.1016/j.bpj.2011.09.060 UR - https://m2.mtmt.hu/api/publication/32122938 ID - 32122938 N1 - Department of Computer Science, University of Oxford, Oxford, United Kingdom Aragón Institute of Engineering Research, IIS Aragón, Universidad de Zaragoza, Zaragoza, Spain Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary Department of Physiology, University of Debrecen, Debrecen, Hungary Export Date: 5 August 2021 CODEN: BIOJA Correspondence Address: Pueyo, E.; Department of Computer Science, , Oxford, United Kingdom; email: epueyo@unizar.es Funding details: TÁMOP-4.2.2-08/1-2008-0013 Funding details: Seventh Framework Programme, FP7, 224381 Funding details: Medical Research Council, MRC, G0700278 Funding details: Royal Society, TEC2010-19410 Funding details: European Commission, EC Funding details: Hungarian Scientific Research Fund, OTKA, TECH_08_A1_CARDIO08 Funding details: Ministerio de Ciencia e Innovación, MICINN, PI 144/2009 Funding details: European Regional Development Fund, FEDER Funding details: Gobierno de Aragón, OTKA CNK-77855 Funding text 1: This study was supported by the European Commission preDiCT grant (DG-INFSO-224381), UK Medical Research Council Career Development Award (B.R.), Royal Society International Joint Project (E.P., B.R.), grant TEC2010-19410 from Ministerio de Ciencia e Innovación, PI 144/2009 and T30 from Gobierno de Aragón, Spain (E.P.), and grants OTKA CNK-77855 from Hungarian Scientific Research Fund, TECH_08_A1_CARDIO08 from National Office Research and Technology–Ányos Jedlik Programme, and TÁMOP-4.2.2-08/1-2008-0013 and TÁMOP-4.2.1/B-09/1/KONV-2010-0005 National Development Agency cofinanced by the European Regional Fund, Hungary (L.V., N.J., T.S., A.V., N.S., P.P.N.). AB - Enhanced temporal and spatial variability in cardiac repolarization has been related to increased arrhythmic risk both clinically and experimentally. Causes and modulators of variability in repolarization and their implications in arrhythmogenesis are however not well understood. At the ionic level, the slow component of the delayed rectifier potassium current (IKs) is an important determinant of ventricular repolarization. In this study, a combination of experimental and computational multiscale studies is used to investigate the role of intrinsic and extrinsic noise in IKs in modulating temporal and spatial variability in ventricular repolarization in human and guinea pig. Results show that under physiological conditions: i), stochastic fluctuations in IKs gating properties (i.e., intrinsic noise) cause significant beat-to-beat variability in action potential duration (APD) in isolated cells, whereas cell-to-cell differences in channel numbers (i.e., extrinsic noise) also contribute to cell-to-cell APD differences; ii), in tissue, electrotonic interactions mask the effect of IKs noise, resulting in a significant decrease in APD temporal and spatial variability compared to isolated cells. Pathological conditions resulting in gap junctional uncoupling or a decrease in repolarization reserve uncover the manifestation of IKs noise at cellular and tissue level, resulting in enhanced ventricular variability and abnormalities in repolarization such as afterdepolarizations and alternans. LA - English DB - MTMT ER - TY - JOUR AU - Bárándi, L AU - Virág, László AU - Jost, Norbert László AU - Horváth, Z AU - Koncz, Istvan AU - Papp, Rita AU - Harmati, Gábor AU - Horváth, Balázs AU - Szentandrássy, Norbert AU - Bányász, Tamás AU - Magyar, János AU - Zaza, A AU - Varró, András AU - Nánási, Péter Pál TI - Reverse rate-dependent changes are determined by baseline action potential duration in mammalian and human ventricular preparations JF - BASIC RESEARCH IN CARDIOLOGY J2 - BASIC RES CARDIOL VL - 105 PY - 2010 IS - 3 SP - 315 EP - 323 PG - 9 SN - 0300-8428 DO - 10.1007/s00395-009-0082-7 UR - https://m2.mtmt.hu/api/publication/1323040 ID - 1323040 N1 - Department of Physiology, University of Debrecen, Nagyerdei krt 98, 4012 Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary Dipartimento di Biotecnologie e Bioscienze, Universita di Milano-Bicocca, Milan, Italy CODEN: BRCAB Correspondence Address: Nánási, P. P.; Department of Physiology, University of Debrecen, Nagyerdei krt 98, 4012 Debrecen, Hungary; email: nanasi@phys.dote.hu Chemicals/CAS: 1 [2 (6 methyl 2 pyridyl)ethyl] 4 (4 methylsulfonylaminobenzoyl)piperidine, 113558-89-7; 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; barium chloride, 10361-37-2; cevadine, 62-59-9; dofetilide, 115256-11-6; lemakalim, 94535-50-9; mexiletine, 31828-71-4, 5370-01-4; sotalol, 3930-20-9, 80456-07-1, 959-24-0; tetrodotoxin, 4368-28-9, 4664-41-9; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, 71145-03-4; Anti-Arrhythmia Agents; Calcium Channel Agonists; Sodium Channel Blockers; Tetrodotoxin, 4368-28-9 AB - Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate-dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for RRD in mammalian ventricular myocardium. Action potentials were recorded using conventional sharp microelectrodes from human, canine, rabbit and guinea pig ventricular myocardium in a rate-dependent manner varying the cycle length (CL) between 0.3 and 5 s. Rate-dependent drug effects were studied using agents known to lengthen or shorten action potentials, and these drug-induced changes in APD were correlated with baseline APD values. Both drug-induced lengthening (by dofetilide, sotalol, E-4031, BaCl2, veratrine, BAY K 8644) and shortening (by mexiletine, tetrodotoxin, lemakalim) of action potentials displayed RRD, i.e., changes in APD were greater at longer than at shorter CLs. In rabbit, where APD is a biphasic function of CL, the drug-induced APD changes were proportional to baseline APD values but not to CL. Similar results were obtained when repolarization was modified by injection of inward or outward current pulses in isolated canine cardiomyocytes. In each case the change in APD was proportional to baseline APD (i.e., that measured before the superfusion of drug or injection of current). Also, the net membrane current (I net), determined from the action potential waveform at the middle of the plateau, was inversely proportional to APD and consequently with to CL. The results indicate that RRD is a common characteristic of all the drugs tested regardless of the modified ion current species. Thus, drug-induced RRD can be considered as an intrinsic property of cardiac membranes based on the inverse relationship between I net and APD. LA - English DB - MTMT ER - TY - JOUR AU - Bányász, Tamás AU - Horváth, Balázs AU - Virág, László AU - Bárándi, L AU - Szentandrássy, Norbert AU - Harmati, Gábor AU - Magyar, János AU - Marangoni, S AU - Zaza, A AU - Varró, András AU - Nánási, Péter Pál TI - Reverse rate dependency is an intrinsic property of canine cardiac preparations JF - CARDIOVASCULAR RESEARCH J2 - CARDIOVASC RES VL - 84 PY - 2009 IS - 2 SP - 237 EP - 244 PG - 8 SN - 0008-6363 DO - 10.1093/cvr/cvp213 UR - https://m2.mtmt.hu/api/publication/1242469 ID - 1242469 N1 - Department of Physiology, University of Debrecen, Nagyerdei krt 98, H-4012 Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary Dipartimento di Biotecnologie e Bioscienze, Universita di Milano-Bicocca, Milano, Italy Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary CODEN: CVREA Correspondence Address: Nánási, P. P.; Department of Physiology, University of Debrecen, Nagyerdei krt 98, H-4012 Debrecen, Hungary; email: nanasi@phys.dote.hu Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; cevadine, 62-59-9; dofetilide, 115256-11-6; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; nicorandil, 65141-46-0; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, 71145-03-4; Anti-Arrhythmia Agents; Barium Compounds; Chlorides; Phenethylamines; Sulfonamides; Veratrine, 62-59-9; barium chloride, 10361-37-2; dofetilide, 115256-11-6 AB - Aims Class III antiarrhythmic agents exhibit reverse rate-dependent lengthening of the action potential duration (APD). In spite of the several theories developed so far to explain this reverse rate dependency (RRD), its mechanism has not yet been clarified. The aim of the present work was to further elucidate the mechanisms responsible for reverse rate-dependent drug effects. Methods and results Action potentials were recorded from multicellular canine ventricular preparations and isolated cardiomyocytes, at cycle lengths (CLs) varying from 0.3 to 5 s, using conventional sharp microelectrodes. APD was either modified by applying inward and outward current pulses, or by superfusion of agents known to lengthen and shorten APD. Net membrane current (Im) was calculated from action potential waveforms. The hypothesis that RRD may be implicit in the relationship between Im and APD was tested by numerical modelling. Both drug-induced lengthening (by veratrine, BAY-K 8644, dofetilide, and BaCl2) and shortening (by lidocaine and nicorandil) of action potentials displayed RRD, i.e. changes in APD were greater at longer than at shorter CL. A similar dependency of effect on CL was found when repolarization was modified by injection of inward or outward current pulses. Im measured at various points during repolarization was inversely proportional to APD and to CL. Model simulations showed that RRD is expected as a consequence of the non-linearity of the relationship between Im and APD. Conclusion RRD of APD modulation is shared, although with differences in magnitude, by interventions of very different nature. RRD can be interpreted as a consequence of the relationship between Im and APD and, as such, is expected in all species having positive APD–CL relationship. This implies that the development of agents prolonging APD with direct rate dependency, or even completely devoid of RRD, may be difficult to achieve. LA - English DB - MTMT ER - TY - CHAP AU - Szentandrássy, Norbert AU - Magyar, János AU - Nánási, Péter Pál ED - Nánási, Péter Pál TI - Electrical inhomogenity in mammalian ventricular myocardium T2 - Advances in Cardiomyocyte Research PB - Transworld Research Network CY - Kerala SN - 9788178954189 PY - 2009 SP - 47 EP - 92 PG - 46 UR - https://m2.mtmt.hu/api/publication/1373239 ID - 1373239 AB - Since the early 80s, when isolation of cardiac myocytes of various origin and application of the whole cell patch clamp technique became commonly used, a tremendous development in our knowledge on the physiology, pharmacology, and biochemistry of cardiac cells have been accumulated. Without attempting of outlining the full cross section of the research area, some hot topics - found peculiarly interesting by the editor and authors of this book - have been chosen to illustrate the progress. Electrophysiological properties of mammalian cardiomyocytes, including intracardial distribution of individual ion channels, kinetic characteristics of ion currents underlying the cardiac action potential, and the experimental techniques used to study these currents, are discussed throughout the first four chapters. As electrical events of the surface membrane may mainly influence cardiac function by modifying intracellular calcium concentration of the myocytes, properties of the dominant determinants of cardiac calcium handling, RyR2 and SERCA2 in the sarcoplasmic reticulum and the Na+/Ca2+ exchanger of the sarcolemma, are analyzed in the subsequent two chapters. Intimate features of force production by the contractile machinery can be also best studied in isolated cardiomyocytes after destruction of their sarcolemma, as shown in Chapter 7. While stress adaptation is a basic mechanism of cardiac survival under pathological conditions, using stem cells in myocardial repair is one of the most promising new therapeutic tools. These perspectives are outlined in the last two chapters. Each of the nine chapters in this book can be considered as a sample of the past, present or future of cardiomyocyte research. The authors and the editor strongly believe that presentation of a new book on the same topic will be soon required - probably within a few years - due to the exponentially increasing research activity in this field. LA - English DB - MTMT ER - TY - JOUR AU - Birinyi, Péter AU - Tóth, András AU - Jóna, István AU - Acsai, Károly AU - Almássy, János AU - Nagy, Norbert AU - Prorok, János AU - Gherasim, I AU - Papp, Zoltán AU - Hertelendi, Zita AU - Szentandrássy, Norbert AU - Bányász, Tamás AU - Fülöp, Ferenc AU - Papp, Gyula AU - Varró, András AU - Nánási, Péter Pál AU - Magyar, János TI - The Na+/Ca2+ exchange blocker SEA0400 fails to enhance cytosolic Ca2+ transient and contractility in canine ventricular cardiomyocytes JF - CARDIOVASCULAR RESEARCH J2 - CARDIOVASC RES VL - 78 PY - 2008 IS - 3 SP - 476 EP - 484 PG - 9 SN - 0008-6363 DO - 10.1093/cvr/cvn031 UR - https://m2.mtmt.hu/api/publication/1125288 ID - 1125288 N1 - Department of Physiology, University of Debrecen, PO Box 22, H-4012 Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, PO Box 427, H-6701 Szeged, Hungary Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, PO Box 427, H-6701 Szeged, Hungary Department of Cardiology, University of Debrecen, PO Box 22, H-4012 Debrecen, Hungary Institute of Pharmaceutical Chemistry, University of Szeged, PO Box 121, H-6701 Szeged, Hungary Cited By :20 Export Date: 3 October 2019 CODEN: CVREA Correspondence Address: Nánási, P. P.; Department of Physiology, University of Debrecen, PO Box 22, H-4012 Debrecen, Hungary; email: nanasi@phys.dote.hu Chemicals/CAS: calcium ion, 14127-61-8; sodium ion, 17341-25-2; caffeine, 30388-07-9, 58-08-2; Aniline Compounds; Caffeine, 58-08-2; Calcium Channels, L-Type; Phenyl Ethers; Ryanodine Receptor Calcium Release Channel; SEA 0400; Sodium-Calcium Exchanger Tradenames: sea 0400 80254 Department of Physiology, University of Debrecen, PO Box 22, H-4012 Debrecen, Hungary Department of Pharmacology and Pharmacotherapy, University of Szeged, PO Box 427, H-6701 Szeged, Hungary Division of Cardiovascular Pharmacology, Hungarian Academy of Sciences, PO Box 427, H-6701 Szeged, Hungary Department of Cardiology, University of Debrecen, PO Box 22, H-4012 Debrecen, Hungary Institute of Pharmaceutical Chemistry, University of Szeged, PO Box 121, H-6701 Szeged, Hungary Cited By :22 Export Date: 31 May 2021 CODEN: CVREA Correspondence Address: Nánási, P. P.; Department of Physiology, PO Box 22, H-4012 Debrecen, Hungary; email: nanasi@phys.dote.hu Chemicals/CAS: calcium ion, 14127-61-8; sodium ion, 17341-25-2; caffeine, 30388-07-9, 58-08-2; Aniline Compounds; Caffeine, 58-08-2; Calcium Channels, L-Type; Phenyl Ethers; Ryanodine Receptor Calcium Release Channel; SEA 0400; Sodium-Calcium Exchanger Tradenames: sea 0400 AB - Aims This study was designed to evaluate the effects of the Na+/Ca2+ exchange (NCX) inhibitor SEA0400 on Ca2+ handling in isolated canine ventricular myocytes. Methods and results Intracellular Ca2+ ([Ca2+](i)) transients, induced by either field stimulation or caffeine flush, were monitored using Ca2+ indicator dyes. [Ca2+](i)-dependent modulation of the inhibitory effect of SEA0400 on NCX was characterized by the changes in Ni2+-sensitive current in voltage-clamped myocytes. Sarcoplasmic reticulum (SR) Ca2+ release and uptake were studied in SIR membrane vesicles. Gating properties of single-ryanodine receptors were analysed in lipid bilayers. Ca2+ sensitivity of the contractile machinery was evaluated in chemically skinned myocytes. In myocytes paced at 1 Hz, neither diastolic [Ca2+](i) nor the amplitude of [Ca2+](i) transients was significantly altered by SEA0400 up to the concentration of 1 mu M, which was shown to inhibit the exchange current. The blocking effect of SEA0400 on NCX decreased with increasing [Ca2+](i), and it was more pronounced in reverse than in forward mode operation at every [Ca2+](i) examined. The rate of decay of the caffeine-induced [Ca2+](i) transients was decreased significantly by 1 mu M SEA0400; however, this effect was only a fraction of that observed with 10 mM NiCl2. Neither SR Ca2+ release and uptake nor cell shortening and Ca2+ sensitivity of the contractile proteins were influenced by SEA0400. Conclusion The lack of any major SEA0400-induced shift in Ca2+ transients or contractility of myocytes can well be explained by its limited inhibitory effect on NCX (further attenuated by elevated [Ca2+](i) levels) and a concomitant reduction in Ca2+ influx due to the predominantly reverse mode blockade of NCX and suppression of L-type Ca2+ current. LA - English DB - MTMT ER - TY - JOUR AU - Bányász, Tamás AU - Magyar, János AU - Szentandrássy, Norbert AU - Horváth, Balázs AU - Birinyi, Péter AU - Szentmiklósi, József András AU - Nánási, Péter Pál TI - Action potential clamp fingerprints of K+ currents in canine cardiomyocytes: their role in ventricular repolarization JF - ACTA PHYSIOLOGICA J2 - ACTA PHYSIOL VL - 190 PY - 2007 IS - 3 SP - 189 EP - 198 PG - 10 SN - 1748-1708 DO - 10.1111/j.1748-1716.2007.01674.x UR - https://m2.mtmt.hu/api/publication/1163715 ID - 1163715 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Gergely AU - Szentandrássy, Norbert AU - Bíró, Tamás AU - Tóth, Balázs István AU - Czifra, Gabriella AU - Magyar, János AU - Bányász, Tamás AU - Varró, András AU - Kovács, László AU - Nánási, Péter Pál TI - Asymmetrical distribution of ion channels in canine and human left-ventricular wall. epicardium versus midmyocardium TS - epicardium versus midmyocardium JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 450 PY - 2005 IS - 5 SP - 307 EP - 316 PG - 10 SN - 0031-6768 DO - 10.1007/s00424-005-1445-z UR - https://m2.mtmt.hu/api/publication/1076727 ID - 1076727 N1 - Megjegyzés-20234210 PubMed ID: 15952036 AB - The aim of the present study was to compare the distribution of ion currents and the major underlying ion channel proteins in canine and human subepicardial (EPI) and midmyocardial (MID) left-ventricular muscle. Ion currents and action potentials were recorded from canine cardiomyocytes derived from the very superficial EPI and central MID regions of the left ventricle. Amplitude, duration and the maximum velocity of depolarization of the action potential were significantly greater in MID than EPI myocytes, whereas phase-1 repolarization was more pronounced in the EPI cells. Amplitudes of the transient outwards K+ current (29.5±1.5 vs. 19.0±2.3 pA/pF at +50 mV) and the slow component of the delayed rectifier K+ current (10.3±2.3 vs. 6.5±1.0 pA/pF at +50 mV) were significantly larger in EPI than in MID myocytes under whole-cell voltage-clamp conditions. The densities of the inwards rectifier K+ current, rapid delayed rectifier K+ current and L-type Ca2+ current were similar in both cell types. Expression of channel proteins in both canine and human ventricular myocardium was determined by Western blotting. In the canine heart, the expression of Kv4.3, Kv1.4, KChIP2 and KvLQT1 was significantly higher, and that of Nav1.5 and MinK much lower, in EPI than in MID. No significant EPI-MID differences were observed in the expression of the other channel proteins studied (Kir2.1, α1C, HERG and MiRP1). Similar results were obtained in human hearts, although the HERG was more abundant in the EPI than in the MID layer. In the canine heart, the EPI-MID differences in ion current densities were proportional to differences in channel protein expression. Except for the density of HERG, the pattern of EPI-MID distribution of ion-channel proteins was identical in canine and human ventricles. LA - English DB - MTMT ER - TY - JOUR AU - Szentandrássy, Norbert AU - Bányász, Tamás AU - Bíró, Tamás AU - Szabó, Gergely AU - Tóth, Balázs István AU - Magyar, János AU - Lázár, József AU - Varró, András AU - Kovács, László AU - Nánási, Péter Pál TI - Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium JF - CARDIOVASCULAR RESEARCH J2 - CARDIOVASC RES VL - 65 PY - 2005 IS - 4 SP - 851 EP - 860 PG - 10 SN - 0008-6363 DO - 10.1016/j.cardiores.2004.11.022 UR - https://m2.mtmt.hu/api/publication/1076734 ID - 1076734 AB - Objectives: The aim of the present study was to compare the apico–basal distribution of ion currents and the underlying ion channel proteins in canine and human ventricular myocardium. Methods: Ion currents and action potentials were recorded in canine cardiomyocytes, isolated from both apical and basal regions of the heart, using whole-cell voltage clamp techniques. Density of channel proteins in canine and human ventricular myocardium was determined by Western blotting. Results: Action potential duration was shorter and the magnitude of phase-1 repolarization was significantly higher in apical than basal canine myocytes. No differences were observed in other parameters of the action potential or cell capacitance. Amplitude of the transient outward K+ current (29.6 ± 5.7 versus 16.5 ± 4.4 pA/pF at +65 mV) and the slow component of the delayed rectifier K+ current (5.61 ± 0.43 versus 2.14 ± 0.18 pA/pF at +50 mV) were significantly larger in apical than in basal myocytes. Densities of the inward rectifier K+ current, rapid delayed rectifier K+ current, and L-type Ca2+ current were similar in myocytes of apical and basal origin. Apico–basal differences were found in the expression of only those channel proteins which are involved in mediation of the transient outward K+ current and the slow delayed rectifier K+ current: expression of Kv1.4, KChIP2, KvLQT1 and MinK was significantly higher in apical than in basal myocardium in both canine and human hearts. Conclusions: The results suggest that marked apico–basal electrical inhomogeneity exists in the canine–and probably in the human–ventricular myocardium, which may result in increased dispersion, and therefore, cannot be ignored when interpreting ECG recordings, pathological alterations, or drug effects. LA - English DB - MTMT ER - TY - JOUR AU - Fülöp, László AU - Bányász, Tamás AU - Magyar, János AU - Szentandrássy, Norbert AU - Varró, András AU - Nánási, Péter Pál TI - Reopening of L-type calcium channels in human ventricular myocytes during applied epicardial action potentials JF - ACTA PHYSIOLOGICA SCANDINAVICA J2 - ACTA PHYSIOL SCAND VL - 180 PY - 2004 IS - 1 SP - 39 EP - 47 PG - 9 SN - 0001-6772 DO - 10.1046/j.0001-6772.2003.01223.x UR - https://m2.mtmt.hu/api/publication/1132568 ID - 1132568 N1 - Department of Physiology, Univ. Medical School of Debrecen, Debrecen, Hungary Dept. Pharmacol. and Pharmacotherapy, University of Szeged, Szeged, Hungary Department of Physiology, University of Debrecen, P.O. Box 22, Debrecen, H-4012, Hungary Cited By :19 Export Date: 3 October 2019 CODEN: APSCA Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, P.O. Box 22, Debrecen, H-4012, Hungary Chemicals/CAS: Calcium Channels, L-Type Department of Physiology, Univ. Medical School of Debrecen, Debrecen, Hungary Dept. Pharmacol. and Pharmacotherapy, University of Szeged, Szeged, Hungary Department of Physiology, University of Debrecen, P.O. Box 22, Debrecen, H-4012, Hungary Cited By :19 Export Date: 4 October 2019 CODEN: APSCA Correspondence Address: Nánási, P.P.; Department of Physiology, University of Debrecen, P.O. Box 22, Debrecen, H-4012, Hungary Chemicals/CAS: Calcium Channels, L-Type Department of Physiology, Univ. Medical School of Debrecen, Debrecen, Hungary Dept. Pharmacol. and Pharmacotherapy, University of Szeged, Szeged, Hungary Department of Physiology, University of Debrecen, P.O. Box 22, Debrecen, H-4012, Hungary Cited By :24 Export Date: 31 May 2021 CODEN: APSCA Correspondence Address: Nánási, P.P.; Department of Physiology, P.O. Box 22, Debrecen, H-4012, Hungary Chemicals/CAS: Calcium Channels, L-Type AB - Aims: Present study was performed to compare the dynamics of human L-type calcium current (I-Ca,I-L) flowing during rectangular voltage pulses, voltage ramps, and action potentials (APs) recorded from epicardiac and endocardiac canine ventricular cells. Methods: I-Ca,I-L was recorded in single myocytes isolated from undiseased human hearts using the whole cell voltage clamp technique. Results: The decay of I-Ca,I-L was monotonic when using rectangular pulses or endocardial APs as voltage commands, whereas the current became double-peaked (displaying a second rise and fall) during epicardial (EPI) APs or voltage ramps used to mimic EPI APs. These I-Ca,I-L profiles were associated with single-hooked and double-hooked phase-plane trajectories, respectively. No sustained current was observed during the AP commands. Kinetics of deactivation and recovery from inactivation of human I-Ca,I-L were determined using twin-pulse voltage protocols and voltage ramps, and the results were similar to those obtained previously in canine cells under identical experimental conditions. Conclusions: I-Ca,I-L can inactivate partially before and deactivate during the phase-1 repolarization of the epicardiac AP, and reopening of these channels seems to be associated with formation of the dome. LA - English DB - MTMT ER - TY - JOUR AU - Bányász, Tamás AU - Fülöp, László AU - Magyar, János AU - Szentandrássy, Norbert AU - Varró, András AU - Nánási, Péter Pál TI - Endocardial versus epicardial differences in L-type calcium current in canine ventricular myocytes studied by action potential voltage clamp JF - CARDIOVASCULAR RESEARCH J2 - CARDIOVASC RES VL - 58 PY - 2003 IS - 1 SP - 66 EP - 75 PG - 10 SN - 0008-6363 DO - 10.1016/S0008-6363(02)00853-2 UR - https://m2.mtmt.hu/api/publication/1132562 ID - 1132562 N1 - Department of Physiology, Univ. Medical School of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary Dept. of Pharmacol./Pharmacotherapy, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary CODEN: CVREA Correspondence Address: Nánási, P.P.; Department of Physiology, Univ. Medical School of Debrecen, P.O. Box 22, H-4012 Debrecen, Hungary; email: nanasi@phys.dote.hu Chemicals/CAS: calcium, 7440-70-2; nisoldipine, 63675-72-9; Calcium Channel Blockers; Calcium Channels, L-Type; Nisoldipine, 63675-72-9 AB - Objectives: The aim of the present study was to assess and compare the dynamics of L-type Ca2+ current (ICa,L) during physiologic action potential (AP) in canine ventricular cardiomyocytes of epicardial (EPI) and endocardial (ENDO) origin. Methods:ICa,L was recorded on cells derived from the two regions of the heart using both AP voltage clamp and conventional whole cell voltage clamp techniques. Results: AP voltage clamp experiments revealed that the decay of ICa,L is monotonic during endocardial AP, whereas the current is double-peaked (displaying a second rise) during epicardial AP. The amplitude of the first peak was significantly greater in ENDO (−4.6±0.8 pA/pF) than in EPI cells (−2.8±0.3 pA/pF). Application of epicardial APs as command pulses to endocardial cells yielded double-peaked ICa,L profiles, and increased the net charge entry carried by ICa,L during the AP from 0.187±0.059 to 0.262±0.056 pC/pF (n = 5, P<0.05). No differences were observed in current densities and inactivation kinetics of ICa,L between EPI and ENDO cells when studied under conventional voltage clamp conditions. Nisoldipine shortened action potentials and eliminated the dome of the epicardial AP. Conclusion: ICa,L was shown to partially inactivate before and deactivate during phase-1 repolarization and reopening of these channels is responsible for the formation of the dome in canine EPI cells. The transmural differences in the profile of ICa,L could be well explained with differences in AP configuration. LA - English DB - MTMT ER - TY - JOUR AU - Fülöp, László AU - Fiák, E AU - Szentandrássy, Norbert AU - Magyar, János AU - Nánási, Péter Pál AU - Bányász, Tamás TI - The role of transmembrane chloride current in afterdepolarisations in canine ventricular cardiomyocytes JF - GENERAL PHYSIOLOGY AND BIOPHYSICS J2 - GEN PHYSIOL BIOPHYS VL - 22 PY - 2003 IS - 3 SP - 341 EP - 353 PG - 13 SN - 0231-5882 UR - https://m2.mtmt.hu/api/publication/1163666 ID - 1163666 AB - The physiological role of chloride currents (Icl) in cardiac cells is poorly understood. The aim of the present study was to reveal the role of Icl in the genesis of early and delayed afterdepolarisations (EADs and DADs, respectively). First we identified Icl under action potential voltage clamp conditions as the anthracene-9-carboxylic acid (ANTRA) (0.5 mmol/l)-sensitive current. The ANTRA-sensitive current was large and outwardly directed at the beginning, while it was moderate and inwardly directed at the end of the action potential. Application of ANTRA under current clamp conditions decreased the depth of the incisura, shifted the plateau upwards and lengthened the duration of action potentials. The effect of ANTRA was studied in three models of afterdepolarisations: the ouabain-induced DAD model, the caesium-induced EAD model, and in the presence of subthreshold concentration of isoproterenol. Preincubation of the cells with 0.5 mmol/l ANTRA failed to induce afterdepolarisations. Ouabain (200 nmol/l) alone caused DADs in 62.5% of the cells within 15 min. When ouabain was applied in the presence of ANTRA, 60% of the myocytes transiently displayed EADs before the development of DADs, and all cells developed DADs within 7 min. Isoproterenol (5 nmol/l) alone failed to induce afterdepolarisations. However, 75% of the cells produced DADs within 6 min when superfused with isoproterenol in the presence of ANTRA. Incubation of the myocytes with 3.6 mmol/l CsCl caused EADs in 71.4% of the cells within 30 min. Application of CsCl in the presence of ANTRA resulted in immediate depolarisation of the membrane from -79.6 +/- 0.4 to -54.2 +/- 3.5 mV. Summarizing our results we conclude that the ANTRA-sensitive current is an important mechanism of defence against afterdepolarisations. Suppression of Icl may thus increase the incidence and accelerate the rate of development of both EADs and DADs. LA - English DB - MTMT ER - TY - JOUR AU - Magyar, János AU - Bányász, Tamás AU - Szigligeti, P AU - Körtvély, Á AU - Jednákovits, A AU - Nánási, Péter Pál TI - Electrophysiological effects of bimoclomol in canine ventricular myocytes JF - NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY J2 - N-S ARCH PHARMACOL VL - 361 PY - 2000 IS - 3 SP - 303 EP - 310 PG - 8 SN - 0028-1298 DO - 10.1007/s002109900164 UR - https://m2.mtmt.hu/api/publication/1163620 ID - 1163620 LA - English DB - MTMT ER - TY - JOUR AU - Szigeti, Gyula Péter AU - Rusznak, Z AU - Kovacs, L AU - Papp, Zoltán TI - Calcium-activated transient membrane currents are carried mainly by chloride ions in isolated atrial, ventricular and Purkinje cells of rabbit heart JF - EXPERIMENTAL PHYSIOLOGY J2 - EXP PHYSIOL VL - 83 PY - 1998 IS - 2 SP - 137 EP - 153 PG - 17 SN - 0958-0670 DO - 10.1113/expphysiol.1998.sp004097 UR - https://m2.mtmt.hu/api/publication/1005465 ID - 1005465 AB - Under physiological conditions, calcium-dependent ([Ca2+](i)-dependent) Cl- currents (I-Cl(Ca)) have been suggested to participate in the repolarizing processes. In this paper, the possible contribution of I-Cl(Ca) to transient inward currents and, hence to arrhythmias, has been studied in myocytes from the working myocardium and from the conductive system. Single atrial, ventricular and Purkinje cells, isolated enzymatically from rabbit heart, have been studied under whole-cell voltage-clamp and were internally perfused with the fluorescent Ca2+ indicator, fura-2 (100 mu M). Ca2+ release from the sarcoplasmic reticulum was either induced by external application of caffeine or occurred spontaneously in Ca2+-overloaded cells. Membrane currents accompanying Ca2+ transients showed linear current-voltage characteristics between -60 and +80 mV as evidenced from fast voltage ramps. When intra- and extracellular Cl- concentrations were kept symmetrical in the absence of the Na+-Ca2+ exchange mechanism, transient currents had a reversal potential close to 0 mV. Reduction of external Cl- concentration shifted this reversal potential towards the new Cl- equilibrium potential. Neither the time course of the transient currents nor the shift in their reversal potentials was significantly affected by the presence of Na+. Approximately 90 % of this current was blocked by the application of the Cl- channel blocker, anthracene-9-carboxylic acid (0.5 mM) at +80 mV. It is concluded, that [Ca2+](i)-activated transient membrane currents in atrial, ventricular and Purkinje cells of rabbit heart are mainly due to the activation of a [Ca2+](i)- dependent Cl- current. LA - English DB - MTMT ER -