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Box 22, Debrecen, H-4012, Hungary \n 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 \n Department of Biomedical Engineering, Genome and Biomedical Science Facility, University of California, Davis, 451 Health Sciences Drive, Rm 2303, Davis, CA 95616, United States \n 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 \n Division of Sport Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary \n Department of Dental Physiology and Pharmacology, Faculty of Dentistry, University of Debrecen, Nagyerdei krt 98, P.O. Box 22, Debrecen, H-4012, Hungary \n Export Date: 8 September 2021 \n CODEN: JMCDA \n Correspondence Address: Nánási, P.P.; Department of Physiology, Nagyerdei krt 98, P.O. Box 22, Hungary; email: nanasi.peter@med.unideb.hu \n Funding details: National Heart, Lung, and Blood Institute, NHLBI, R01HL090880, R01HL123526 \n Funding details: Magyar Tudományos Akadémia, MTA \n Funding text 1: The authors thank Miss ?va S?gi for her excellent technical assistance. 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false, "published" : true, "oldId" : 1316479, "snippet" : true }, "volume" : "109", "firstPage" : "27", "lastPage" : "37", "firstPageOrInternalIdForSort" : "27", "pageLength" : 11, "publishedYear" : 2017, "abstractText" : "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.", "subjects" : [ { "otype" : "Classification", "mtid" : 12125, "link" : "/api/classification/12125", "label" : "Általános orvostudomány", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 10545, "link" : "/api/classification/10545", "label" : "Biológiai tudományok", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 12208, "link" : "/api/classification/12208", "label" : "Fiziológia (benne citológia)", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 12215, "link" : "/api/classification/12215", "label" : "Klinikai orvostan", "published" : true, "snippet" : true }, { "otype" : "Classification", "mtid" : 12124, "link" : "/api/classification/12124", "label" : "Orvos- és egészségtudomány", "published" : true, "snippet" : true } ], "fundings" : [ { 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