Mohammed, Aiman and Demeter-Haludka, Vivien and Abdelmagid, Alaa Amin Elmubarak and Topal, Leila and Naveed, Muhammad and Mohácsi, Gábor and Paskuj, Benjámin and Bitay, Gergő and Kohajda, Zsófia and Benke, Kálmán and Sayour, Alex Ali and Radovits, Tamás and Bitay, Miklós and Virág, László and Jost, Norbert László and Baczkó, István and Varró, András and Merkely, Béla Péter and Nagy, Norbert (2026) Do small-conductance Ca2+-activated K+-channels contribute to ventricular repolarization in human heart failure? AMERICAN JOURNAL OF PHYSIOLOGY: HEART AND CIRCULATORY PHYSIOLOGY, 330 (6). H1935-H1950. ISSN 0363-6135
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Abstract
Chronic heart failure constitutes a clinical syndrome characterized by substantial attenuation of repolarization reserve resulting from electrical remodeling. The small-conductance Ca2+-activated K+ channel (SK) has been reported to undergo upregulation in animal heart failure models and in human preparations, however its exact function is not fully understood. This study aims to elucidate the functional role of SK channels in end-stage human heart failure. SK-protein expression of undiseased and failed human ventricular tissue was investigated by Western-blot technique. Action potentials were measured by standard microelectrode technique from right ventricular papillary muscles of undiseased hearts and from right and left papillary muscles and from left midmyocardial tissue slices of failing hearts. Ionic currents were recorded by the whole-cell configuration of the patch-clamp technique on isolated cells obtained from left ventricles of failing hearts. Failing hearts exerted consistent action potential lengthening and lacked spike-and-dome compared to undiseased hearts. Western-blot revealed identical SK-expression between undiseased and failing hearts. 100 nM apamin, a commonly used selective SK-channel inhibitor, failed to alter action potential duration values of the failing hearts in left and right endocardial preparations and in left midmyocardium. Furthermore, no apamin sensitive current was identified in isolated cells. It was found weak coupling between SK2-channels and L-type Ca2+ channels. These results do not confirm the results of previous studies claiming an important role of SK-channels in the repolarization of human failing heart.
| Item Type: | Article |
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| Additional Information: | Funding Agency and Grant Number: National Research Development and Innovation Office [NKFIH K 135464, K 142738, 150395, GINOP-2.3.2.-15-2016-00006, GINOP-2.3.2.-15-2016-00047, FK-142949, STARTING-150884, K-147212, GINOP-2.3.2.-15-2016-00040, TKP2021-EGA-32]; Ministry of Human Capacities Hungary [EFOP-3.6.2-16-2017-00006]; Albert Szent-Gyorgyi Medical School institutional [SZTEAOK-KKA 2021]; Hungarian Research Network HUN-REN TKI project; National Heart Laboratory, Hungary [RRF-2.3.1-21-2022-00003]; European Union; Pharmaceutical and Medical Device Developments Competence Centre of the Life Sciences Cluster of the Centre of Excellence for Interdisciplinary Research; Development and Innovation of the University of Szeged, Hungary; Hungarian Academy of Sciences Janos Bolyai Scholarship; University of Szeged Open Access Fund [8680] Funding text: This work was supported by the National Research Development and Innovation Office Grants NKFIH K 135464, K 142738,ADVANCED 150395, GINOP-2.3.2.-15-2016-00006, and GINOP-2.3.2.-15-2016-00047 (to A.V. and N.J.); FK-142949 (to N.N. and Z.K.);STARTING-150884 (to Z.K.); K-147212, GINOP-2.3.2.-15-2016-00040,and TKP2021-EGA-32 (to I.B.), the Ministry of Human Capacities Hungary Grant EFOP-3.6.2-16-2017-00006 (to A.V., N.J., and I.B.),the Albert Szent-Gyorgyi Medical School institutional grant SZTEAOK-KKA 2021 (to L.V.), SZTE AOK-KKA 2022 (to N.J.) and SZTEAOK-KKA 2024 (to I.B.) and by Hungarian Research Network HUN-REN TKI project (to Z.K., A.V., and N.J.). This study was also sup-ported by Project RRF-2.3.1-21-2022-00003"National Heart Laboratory, Hungary" implemented with the support provided by the European Union (to I.B. and B.M.) and by the Pharmaceutical and Medical Device Developments Competence Centre of the Life Sciences Cluster of the Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged, Hungary. The study was further supported by the Hungarian Academy of Sciences Janos Bolyai Scholarship (to Z.K.). The study was further supported by the University of Szeged Open Access Fund, Grant ID: 8680. |
| Uncontrolled Keywords: | action potential; Arrhythmia; heart failure; apamin; SK-channel; |
| Subjects: | R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 17 Sep 2026 14:21 |
| Last Modified: | 17 Sep 2026 14:21 |
| URI: | https://real.mtak.hu/id/eprint/246625 |
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