@article{MTMT:3099238, title = {7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome}, url = {https://m2.mtmt.hu/api/publication/3099238}, author = {Balajthy, András and Somodi, Sándor and Pethő, Z and Péter, Mária and Varga, Zoltán and P. Szabó, Gabriella and Paragh, György and Vigh, László and Panyi, György and Hajdu, Péter Béla}, doi = {10.1007/s00424-016-1851-4}, journal-iso = {PFLUG ARCH EUR J PHY}, journal = {PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY}, volume = {468}, unique-id = {3099238}, issn = {0031-6768}, abstract = {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.}, keywords = {cholesterol; Kv1.3; 7-Dehydrocholesterol; Smith-Lemli-Opitz syndrome; Voltage-gated ion channel}, year = {2016}, eissn = {1432-2013}, pages = {1403-1418}, orcid-numbers = {Somodi, Sándor/0000-0002-3615-2300; Panyi, György/0000-0001-6227-3301} } @article{MTMT:2239256, title = {Analysis of the K+ current in human CD4+ T lymphocytes in hypercholesterolemic state}, url = {https://m2.mtmt.hu/api/publication/2239256}, author = {Somodi, Sándor and Balajthy, András and Szilágyi, Orsolya and Pethő, Zoltán Dénes and Harangi, Mariann and Paragh, György and Panyi, György and Hajdu, Péter Béla}, doi = {10.1016/j.cellimm.2013.01.004}, journal-iso = {CELL IMMUNOL}, journal = {CELLULAR IMMUNOLOGY}, volume = {281}, unique-id = {2239256}, issn = {0008-8749}, abstract = {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.}, keywords = {PROLIFERATION; cholesterol; T lymphocyte; Kv1.3}, year = {2013}, eissn = {1090-2163}, pages = {20-26}, orcid-numbers = {Somodi, Sándor/0000-0002-3615-2300; Panyi, György/0000-0001-6227-3301} } @article{MTMT:2273474, title = {The role of PSD-95 in the rearrangement of Kv1.3 channels to the immunological synapse}, url = {https://m2.mtmt.hu/api/publication/2273474}, author = {Szilágyi, Orsolya and Boratkó, Anita and Panyi, György and Hajdu, Péter Béla}, doi = {10.1007/s00424-013-1256-6}, journal-iso = {PFLUG ARCH EUR J PHY}, journal = {PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY}, volume = {465}, unique-id = {2273474}, issn = {0031-6768}, year = {2013}, eissn = {1432-2013}, pages = {1341-1353}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:1321720, title = {Functional consequences of Kv1.3 ion channel rearrangement into the immunological synapse.}, url = {https://m2.mtmt.hu/api/publication/1321720}, author = {Tóth, Ágnes and Szilágyi, Orsolya and Krasznai, Zoltán and Panyi, György and Hajdu, Péter Béla}, doi = {10.1016/j.imlet.2009.05.004}, journal-iso = {IMMUNOL LETT}, journal = {IMMUNOLOGY LETTERS}, volume = {125}, unique-id = {1321720}, issn = {0165-2478}, abstract = {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.}, year = {2009}, eissn = {1879-0542}, pages = {15-21}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:1265715, title = {Developmental switch of the expression of ion channels in human dendritic cells.}, url = {https://m2.mtmt.hu/api/publication/1265715}, author = {Zsiros, E and Kis-Tóth, Katalin and Hajdu, Péter Béla and Gáspár, Rezső and Bielanska, J and Felipe, A and Rajnavölgyi, Éva and Panyi, György}, doi = {10.4049/jimmunol.0803003}, journal-iso = {J IMMUNOL}, journal = {JOURNAL OF IMMUNOLOGY}, volume = {183}, unique-id = {1265715}, issn = {0022-1767}, abstract = {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.}, year = {2009}, eissn = {1550-6606}, pages = {4483-4492}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:105638, title = {Ion channels and lymphocyte activation}, url = {https://m2.mtmt.hu/api/publication/105638}, author = {Panyi, György and Varga, Zoltán and Gaspar, R}, doi = {10.1016/j.imlet.2003.11.020}, journal-iso = {IMMUNOL LETT}, journal = {IMMUNOLOGY LETTERS}, volume = {92}, unique-id = {105638}, issn = {0165-2478}, year = {2004}, eissn = {1879-0542}, pages = {55-66}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:1075641, title = {Kv1.3 potassium channels are localized in the immunological synapse formed between cytotoxic and target cells}, url = {https://m2.mtmt.hu/api/publication/1075641}, author = {Panyi, György and Vámosi, György and Bacsó, Zsolt and Bagdány, M and Bodnár, Andrea and Varga, Zoltán and Gáspár, Rezső and Mátyus, László and Damjanovich, Sándor}, doi = {10.1073/pnas.0307421100}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {101}, unique-id = {1075641}, issn = {0027-8424}, year = {2004}, eissn = {1091-6490}, pages = {1285-1290}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:105647, title = {Cholesterol modifies the gating of Kv1.3 in human T lymphocytes}, url = {https://m2.mtmt.hu/api/publication/105647}, author = {Hajdu, Péter Béla and Varga, Zoltán and Pieri, C and Panyi, György and Gáspár, Rezső}, doi = {10.1007/s00424-002-0974-y}, journal-iso = {PFLUG ARCH EUR J PHY}, journal = {PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY}, volume = {445}, unique-id = {105647}, issn = {0031-6768}, year = {2003}, eissn = {1432-2013}, pages = {674-682}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:105648, title = {Colocalization and nonrandom distribution of Kv1.3 potassium channels and CD3 molecules in the plasma membrane of human T lymphocytes}, url = {https://m2.mtmt.hu/api/publication/105648}, author = {Panyi, György and Bagdány, Miklós and Bodnár, Andrea and Vámosi, György and Szentesi, Gergely and Jenei, Attila and Mátyus, László and Varga, S and Waldmann, TA and Gáspár, Rezső and Damjanovich, Sándor}, doi = {10.1073/pnas.0438057100}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {100}, unique-id = {105648}, issn = {0027-8424}, abstract = {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.}, year = {2003}, eissn = {1091-6490}, pages = {2592-2597}, orcid-numbers = {Panyi, György/0000-0001-6227-3301} } @article{MTMT:1863338, title = {Alteration of lymphocyte membrane phospholipids and intracellular free calcium concentrations in hyperlipidemic subjects.}, url = {https://m2.mtmt.hu/api/publication/1863338}, author = {Seres, Ildikó and Freyss-Beguin, M and Mohácsi, Attila and Kozlovsky, B and Simon, J and Devynck, MA and Fulop, T Jr}, doi = {10.1016/0021-9150(95)05714-5}, journal-iso = {ATHEROSCLEROSIS}, journal = {ATHEROSCLEROSIS}, volume = {121}, unique-id = {1863338}, issn = {0021-9150}, abstract = {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.}, keywords = {Female; Middle Aged; Male; Humans; Spectrometry, Fluorescence; Cholesterol/metabolism; Fatty Acids/metabolism; Membrane Lipids/*metabolism; Calcium/*metabolism; Phospholipids/*metabolism; Lymphocytes/*metabolism; Thymidine/diagnostic use; Intracellular Fluid/*metabolism; Hypercholesterolemia/*metabolism}, year = {1996}, eissn = {1879-1484}, pages = {175-183} }