Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes

Shenghui Liang, Quanyi Wang, Weiwei Zhang, Hailin Zhang, Shengjiang Tan, Asif Ahmed, Yuchun Gu*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Reperfusion-induced ventricular fibrillation (VF) severely threatens the lives of post-myocardial infarction patients. Carbon monoxide (CO) - produced by haem oxygenase in cardiomyocytes - has been reported to prevent VF through an unknown mechanism of action. Here, we report that CO prolongs action potential duration (APD) by inhibiting a subset of inward-rectifying potassium (Kir) channels. We show that CO blocks Kir2.2 and Kir2.3 but not Kir2.1 channels in both cardiomyocytes and HEK-293 cells transfected with Kir. CO directly inhibits Kir2.3 by interfering with its interaction with the second messenger phosphatidylinositol (4,5)-bisphosphate (PIP 2). As the inhibition of Kir2.2 and Kir2.3 by CO prolongs APD in myocytes, cardiac Kir2.2 and Kir2.3 are promising targets for the prevention of reperfusion-induced VF.

Original languageEnglish
Article number4676
Number of pages7
JournalNature Communications
Volume5
Early online date14 Aug 2014
DOIs
Publication statusPublished - 2014

Bibliographical note

Funding: National Key Basic Research Program of China No. 2013CB531200/6, 973 Project No. 2013CB531206 and NSF No.81170236); British Heart Foundation (RG/09/001/25940); and Medical Research Council (G0700288).

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