School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
Division of Cardiovascular and Diabetes Research, LICAMM, Faculty of Medicine and Health, University of Leeds, Leeds, LS2 9JT, UK.
Commun Biol. 2023 Jun 19;6(1):651. doi: 10.1038/s42003-023-05016-5.
The voltage-gated K channel plays a key role in atrial excitability, conducting the ultra-rapid rectifier K current (I) and contributing to the repolarization of the atrial action potential. In this study, we examine its regulation by hydrogen sulfide (HS) in HL-1 cardiomyocytes and in HEK293 cells expressing human Kv1.5. Pacing induced remodeling resulted in shorting action potential duration, enhanced both Kv1.5 channel and HS producing enzymes protein expression in HL-1 cardiomyocytes. HS supplementation reduced these remodeling changes and restored action potential duration through inhibition of Kv1.5 channel. HS also inhibited recombinant hKv1.5, lead to nitric oxide (NO) mediated S-nitrosylation and activated endothelial nitric oxide synthase (eNOS) by increased phosphorylation of Ser1177, prevention of NO formation precluded these effects. Regulation of I by HS has important cardiovascular implications and represents a novel and potential therapeutic target.
电压门控钾通道在心房兴奋性中起着关键作用，传导超快速整流钾电流 (I)，并有助于心房动作电位的复极化。在这项研究中，我们研究了其在 HL-1 心肌细胞和表达人 Kv1.5 的 HEK293 细胞中的调节。起搏诱导的重构导致动作电位时程缩短，增强了 HL-1 心肌细胞中的 Kv1.5 通道和产生 HS 的酶的蛋白表达。HS 补充减少了这些重构变化，并通过抑制 Kv1.5 通道恢复了动作电位时程。HS 还抑制重组 hKv1.5，导致一氧化氮 (NO) 介导的 S-亚硝基化，并通过 Ser1177 的磷酸化增加激活内皮型一氧化氮合酶 (eNOS)，阻止 NO 形成则会排除这些作用。HS 对 I 的调节对心血管系统有重要意义，代表了一种新的潜在治疗靶点。
