Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes

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

doi:10.1038/ncomms5676

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 journal › Article › peer-review

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 language	English
Article number	4676
Number of pages	7
Journal	Nature Communications
Volume	5
Early online date	14 Aug 2014
DOIs	https://doi.org/10.1038/ncomms5676
Publication status	Published - 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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@article{5251927c42264dc38013561e9867856b,

title = "Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes",

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.",

author = "Shenghui Liang and Quanyi Wang and Weiwei Zhang and Hailin Zhang and Shengjiang Tan and Asif Ahmed and Yuchun Gu",

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).",

year = "2014",

doi = "10.1038/ncomms5676",

language = "English",

volume = "5",

journal = "Nature Communications",

issn = "2041-1723",

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T1 - Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes

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).

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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UR - https://www.nature.com/articles/ncomms5676

U2 - 10.1038/ncomms5676

DO - 10.1038/ncomms5676

M3 - Article

AN - SCOPUS:84907337791

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4676

ER -

Carbon monoxide inhibits inward rectifier potassium channels in cardiomyocytes

Abstract

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