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

Fingerprint

Inwardly Rectifying Potassium Channel
rectifiers
Carbon Monoxide
Cardiac Myocytes
carbon monoxide
fibrillation
Ventricular Fibrillation
Action Potentials
Reperfusion
myocardial infarction
Heme Oxygenase (Decyclizing)
muscle cells
HEK293 Cells
Potassium Channels
Second Messenger Systems
Phosphatidylinositols
set theory
Potassium
Myocardial Infarction
cells

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).

Cite this

Liang, Shenghui ; Wang, Quanyi ; Zhang, Weiwei ; Zhang, Hailin ; Tan, Shengjiang ; Ahmed, Asif ; Gu, Yuchun. / Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes. In: Nature Communications. 2014 ; Vol. 5.
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Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes. / Liang, Shenghui; Wang, Quanyi; Zhang, Weiwei; Zhang, Hailin; Tan, Shengjiang; Ahmed, Asif; Gu, Yuchun.

In: Nature Communications, Vol. 5, 4676, 2014.

Research output: Contribution to journalArticle

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AU - Liang, Shenghui

AU - Wang, Quanyi

AU - Zhang, Weiwei

AU - Zhang, Hailin

AU - Tan, Shengjiang

AU - Ahmed, Asif

AU - Gu, Yuchun

N1 - 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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