TY - JOUR AU - Balajthy, András AU - Somodi, Sándor AU - Pethő, Z AU - Péter, Mária AU - Varga, Zoltán AU - P. Szabó, Gabriella AU - Paragh, György AU - Vigh, László AU - Panyi, György AU - Hajdu, Péter Béla TI - 7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 468 PY - 2016 IS - 8 SP - 1403 EP - 1418 PG - 16 SN - 0031-6768 DO - 10.1007/s00424-016-1851-4 UR - https://m2.mtmt.hu/api/publication/3099238 ID - 3099238 AB - In vitro manipulation of membrane sterol level affects the regulation of ion channels and consequently certain cellular functions; however, a comprehensive study that confirms the pathophysiological significance of these results is missing. The malfunction of 7-dehydrocholesterol (7DHC) reductase in Smith-Lemli-Opitz syndrome (SLOS) leads to the elevation of the 7-dehydrocholesterol level in the plasma membrane. T lymphocytes were isolated from SLOS patients to assess the effect of the in vivo altered membrane sterol composition on the operation of the voltage-gated Kv1.3 channel and the ion channel-dependent mitogenic responses. We found that the kinetic and equilibrium parameters of Kv1.3 activation changed in SLOS cells. Identical changes in Kv1.3 operation were observed when control/healthy T cells were loaded with 7DHC. Removal of the putative sterol binding sites on Kv1.3 resulted in a phenotype that was not influenced by the elevation in membrane sterol level. Functional assays exhibited impaired activation and proliferation rate of T cells probably partially due to the modified Kv1.3 operation. We concluded that the altered membrane sterol composition hindered the operation of Kv1.3 as well as the ion channel-controlled T cell functions. © 2016, Springer-Verlag Berlin Heidelberg. LA - English DB - MTMT ER - TY - JOUR AU - Somodi, Sándor AU - Balajthy, András AU - Szilágyi, Orsolya AU - Pethő, Zoltán Dénes AU - Harangi, Mariann AU - Paragh, György AU - Panyi, György AU - Hajdu, Péter Béla TI - Analysis of the K+ current in human CD4+ T lymphocytes in hypercholesterolemic state JF - CELLULAR IMMUNOLOGY J2 - CELL IMMUNOL VL - 281 PY - 2013 IS - 1 SP - 20 EP - 26 PG - 7 SN - 0008-8749 DO - 10.1016/j.cellimm.2013.01.004 UR - https://m2.mtmt.hu/api/publication/2239256 ID - 2239256 N1 - 162058 AB - Atherosclerosis involves immune mechanisms: T lymphocytes are found in atherosclerotic plaques, suggesting their activation during atherogenesis. The predominant voltage-gated potassium channel of T cells, Kv1.3 is a key regulator of the Ca2+-dependent activation pathway. In the present experiments we studied the proliferation capacity and functional changes of Kv1.3 channels in T cells from healthy and hypercholestaeremic patients.By means of CFSE-assay (carboxyfluorescein succinimidyl ester) we showed that spontaneous activation rate of lymphocytes in hypercholesterolemia was elevated and the antiCD3/antiCD28 co-stimulation was less effective as compared to the healthy group. Using whole-cell patch-clamping we obtained that the activation and deactivation kinetics of Kv1.3 channels were faster in hypercholesterolemic state but no change in other parameters of Kv1.3 were found (inactivation kinetics, steady-state activation, expression level). We suppose that incorporation of oxLDL species via its raft-rupturing effect can modify proliferative rate of T cells as well as the gating of Kv1.3 channels. © 2013 Elsevier Inc. LA - English DB - MTMT ER - TY - JOUR AU - Szilágyi, Orsolya AU - Boratkó, Anita AU - Panyi, György AU - Hajdu, Péter Béla TI - The role of PSD-95 in the rearrangement of Kv1.3 channels to the immunological synapse JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 465 PY - 2013 IS - 9 SP - 1341 EP - 1353 PG - 13 SN - 0031-6768 DO - 10.1007/s00424-013-1256-6 UR - https://m2.mtmt.hu/api/publication/2273474 ID - 2273474 N1 - WoS:hiba:000323436300010 2019-03-08 21:58 első szerző nem egyezik LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Ágnes AU - Szilágyi, Orsolya AU - Krasznai, Zoltán AU - Panyi, György AU - Hajdu, Péter Béla TI - Functional consequences of Kv1.3 ion channel rearrangement into the immunological synapse. JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 125 PY - 2009 IS - 1 SP - 15 EP - 21 PG - 7 SN - 0165-2478 DO - 10.1016/j.imlet.2009.05.004 UR - https://m2.mtmt.hu/api/publication/1321720 ID - 1321720 N1 - CIN: Immunol Lett. 2009 Aug 15;125(2):156-7. PMID: 19595706 AB - Formation of immunological synapse (IS), the interface between T cells and antigen presenting cells, is a crucial step in T cell activation. This conjugation formation results in the rearrangement and segregation of a set of membrane bound and cytosolic proteins, including that of the T cell receptor, into membrane domains. It was showed earlier that Kv1.3, the dominant voltage-gated potassium channel of T cells redistributes into the IS on interaction with its specific APC. In the present experiments we investigated the functional consequences of the translocation of Kv1.3 channels into the IS formed between mouse helper T (T(h)2) and B cells. Biophysical characteristics of whole-cell Kv1.3 current in standalone cells (c) or ones in IS (IS) were determined using voltage-clamp configuration of standard whole-cell patch-clamp technique. Patch-clamp recordings showed that the activation of Kv1.3 current slowed (tau(a,IS)=2.36+/-0.13 ms (n=7); tau(a,c)=1.36+/-0.06 ms (n=18)) whereas the inactivation rate increased (tau(i,IS)=263+/-29 ms (n=7); tau(i,c)=365+/-27 ms (n=17)) in cells being in IS compared to the standalone cells. The equilibrium distribution between the open and the closed states of Kv1.3 (voltage-dependence of steady-state activation) was shifted toward the depolarizing potentials in T cells engaged into IS (V(1/2,IS)=-20.9+/-2 mV (n=7), V(1/2,c)=-26.4+/-1.5 mV (n=12)). Thus, segregation of Kv1.3 channels into the IS modifies the gating properties of the channels. Application of protein kinase (PK) inhibitors (PKC: GF109203X, PKA: H89, p56Lck: damnacanthal) demonstrated that increase in the inactivation rate can be explained by the dephosphorylation of the channel protein. However, the slower activation kinetics of Kv1.3 in IS is likely to be the consequence of the redistribution of the channels into distinct membrane domains. LA - English DB - MTMT ER - TY - JOUR AU - Zsiros, E AU - Kis-Tóth, Katalin AU - Hajdu, Péter Béla AU - Gáspár, Rezső AU - Bielanska, J AU - Felipe, A AU - Rajnavölgyi, Éva AU - Panyi, György TI - Developmental switch of the expression of ion channels in human dendritic cells. JF - JOURNAL OF IMMUNOLOGY J2 - J IMMUNOL VL - 183 PY - 2009 IS - 7 SP - 4483 EP - 4492 PG - 10 SN - 0022-1767 DO - 10.4049/jimmunol.0803003 UR - https://m2.mtmt.hu/api/publication/1265715 ID - 1265715 AB - Modulation of the expression and activity of plasma membrane ion channels is one of the mechanisms by which immune cells can regulate their intracellular Ca(2+) signaling pathways required for proliferation and/or differentiation. Voltage-gated K+ channels, inwardly rectifying K+ channels, and Ca(2+)-activated K+ channels have been described to play a major role in controlling the membrane potential in lymphocytes and professional APCs, such as monocytes, macrophages, and dendritic cells (DCs). Our study aimed at the characterization and identification of ion channels expressed in the course of human DC differentiation from monocytes. We report in this study for the first time that immature monocyte-derived DCs express voltage-gated Na+ channels in their plasma membrane. The analysis of the biophysical and pharmacological properties of the current and PCR-based cloning revealed the presence of Nav1.7 channels in immature DCs. Transition from the immature to a mature differentiation state, however, was accompanied by the down-regulation of Nav1.7 expression concomitant with the up- regulation of voltage-gated Kv1.3 K+ channel expression. The presence of Kv1.3 channels seems to be common for immune cells; hence, selective Kv1.3 blockers may emerge as candidates for inhibiting various functions of mature DCs that involve their migratory, cytokine-secreting, and T cell-activating potential. LA - English DB - MTMT ER - TY - JOUR AU - Panyi, György AU - Varga, Zoltán AU - Gaspar, R TI - Ion channels and lymphocyte activation JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 92 PY - 2004 SP - 55 EP - 66 PG - 12 SN - 0165-2478 DO - 10.1016/j.imlet.2003.11.020 UR - https://m2.mtmt.hu/api/publication/105638 ID - 105638 LA - English DB - MTMT ER - TY - JOUR AU - Panyi, György AU - Vámosi, György AU - Bacsó, Zsolt AU - Bagdány, M AU - Bodnár, Andrea AU - Varga, Zoltán AU - Gáspár, Rezső AU - Mátyus, László AU - Damjanovich, Sándor TI - Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 101 PY - 2004 IS - 5 SP - 1285 EP - 1290 PG - 6 SN - 0027-8424 DO - 10.1073/pnas.0307421100 UR - https://m2.mtmt.hu/api/publication/1075641 ID - 1075641 N1 - Panyi G, Vamosi G, Bacso Z are equal first authors LA - English DB - MTMT ER - TY - JOUR AU - Hajdu, Péter Béla AU - Varga, Zoltán AU - Pieri, C AU - Panyi, György AU - Gáspár, Rezső TI - Cholesterol modifies the gating of Kv1.3 in human T lymphocytes JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 445 PY - 2003 IS - 6 SP - 674 EP - 682 PG - 9 SN - 0031-6768 DO - 10.1007/s00424-002-0974-y UR - https://m2.mtmt.hu/api/publication/105647 ID - 105647 LA - English DB - MTMT ER - TY - JOUR AU - Panyi, György AU - Bagdány, Miklós AU - Bodnár, Andrea AU - Vámosi, György AU - Szentesi, Gergely AU - Jenei, Attila AU - Mátyus, László AU - Varga, S AU - Waldmann, TA AU - Gáspár, Rezső AU - Damjanovich, Sándor TI - Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 100 PY - 2003 SP - 2592 EP - 2597 PG - 6 SN - 0027-8424 DO - 10.1073/pnas.0438057100 UR - https://m2.mtmt.hu/api/publication/105648 ID - 105648 AB - Distribution and lateral organization of Kv1.3 potassium channels and CD3 molecules were studied by using electron microscopy, confocal laser scanning microscopy, and fluorescence resonance energy transfer. Immunogold labeling and electron microscopy showed that the distribution of FLAG epitope-tagged Kv1.3 channels (Kv1.3/FLAG) significantly differs from the stochastic Poisson distribution in the plasma membrane of human T lymphoma cells. Confocal laser scanning microscopy images showed that Kv1.3/FLAG channels and CD3 molecules accumulated in largely overlapping membrane areas. The numerical analysis of crosscorrelation of the spatial intensity distributions yielded a high correlation coefficient (C = 0.64). A different hierarchical level of molecular proximity between Kv1.3/FLAG and CD3 proteins was reported by a high fluorescence resonance energy transfer efficiency (E = 51%). These findings implicate that reciprocal regulation of ion-channel activity, membrane potential, and the function of receptor complexes may contribute to the proper functioning of the immunological synapse. LA - English DB - MTMT ER - TY - JOUR AU - Seres, Ildikó AU - Freyss-Beguin, M AU - Mohácsi, Attila AU - Kozlovsky, B AU - Simon, J AU - Devynck, MA AU - Fulop, T Jr TI - Alteration of lymphocyte membrane phospholipids and intracellular free calcium concentrations in hyperlipidemic subjects. JF - ATHEROSCLEROSIS J2 - ATHEROSCLEROSIS VL - 121 PY - 1996 IS - 2 SP - 175 EP - 183 PG - 9 SN - 0021-9150 DO - 10.1016/0021-9150(95)05714-5 UR - https://m2.mtmt.hu/api/publication/1863338 ID - 1863338 N1 - Megjegyzés-26671259 Megjegyzés-22053828 Z9: 8 Megjegyzés-22043980 Z9: 8 AB - Hypercholesterolemia has been proposed to influence cell functions via changes in membrane composition. The aim of the present study was to determine whether the membrane phospholipid composition of human lymphocytes is modified in hypercholesterolemia and whether these changes are accompanied by functional modifications. The phospholipid fatty acid contents and intracellular free calcium concentrations were determined in peripheral blood lymphocytes from 13 subjects with serum total cholesterol levels ranging from 4.6 to 8.8 mmol/l. The spontaneous basal rate of thymidine incorporation in lymphocyte of hypercholesterolemic individuals increased, while its relative stimulation by ConA was less effective. Important changes in membrane lipid composition, consisting mainly of decrease of the mass of phospholipids, and of associated polyunsaturated fatty acids were observed in hypercholesterolemia. In contrast, the cell cholesterol content was significantly increased. The intracellular free calcium concentration was enhanced and strongly associated with circulating cholesterol levels, cell cholesterol content and phospholipid fatty acids. These results indicate that hypercholesterolemia is accompanied by profound changes in lymphocyte membrane lipid composition and Ca(2+) handling. LA - English DB - MTMT ER -