Hydrogen Sulfide Targets the Cys320/Cys529 Motif in Kv4.2 to Inhibit the Ito Potassium Channels in Cardiomyocytes and Regularizes Fatal Arrhythmia in Myocardial Infarction

Antioxidants & Redox Signaling
Shan-Feng MaYi-Chun Zhu

Abstract

The mechanisms underlying numerous biological roles of hydrogen sulfide (H2S) remain largely unknown. We have previously reported an inhibitory role of H2S in the L-type calcium channels in cardiomyocytes. This prompts us to examine the mechanisms underlying the potential regulation of H2S on the ion channels. H2S showed a novel inhibitory effect on Ito potassium channels, and this effect was blocked by mutation at the Cys320 and/or Cys529 residues of the Kv4.2 subunit. H2S broke the disulfide bridge between a pair of oxidized cysteine residues; however, it did not modify single cysteine residues. H2S extended action potential duration in epicardial myocytes and regularized fatal arrhythmia in a rat model of myocardial infarction. H2S treatment significantly increased survival by ∼1.4-fold in the critical 2-h time window after myocardial infarction with a protection against ventricular premature beats and fatal arrhythmia. However, H2S did not change the function of other ion channels, including IK1 and INa. H2S targets the Cys320/Cys529 motif in Kv4.2 to regulate the Ito potassium channels. H2S also shows a potent regularizing effect against fatal arrhythmia in a rat model of myocardial infarction. The study provides the first...Continue Reading

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Citations

Apr 9, 2016·Oxidative Medicine and Cellular Longevity·Na LiYi-Chun Zhu
Feb 6, 2017·American Journal of Physiology. Cell Physiology·Nancy L KanagyAndreas Papapetropoulos
Apr 18, 2019·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·You En ZhangJie Liu
May 2, 2019·Frontiers in Pharmacology·Yiya ZhangXiongzhi Zeng
Feb 26, 2016·Journal of Hematology & Oncology·Huan-Di LiuYi-Chun Zhu
Nov 18, 2021·American Journal of Physiology. Cell Physiology·Adriana M Fresquez, Carl White

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Methods Mentioned

BETA
Confocal microscopy
transfection
enzymatic dissociation

Software Mentioned

Clampfit
Origin

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