Reduction in number of sarcolemmal K ATP channels slows cardiac action potential duration shortening under hypoxia

Zhiyong Zhu; Colin M-L Burnett; Gennadiy Maksymov; Elizabeth Stepniak; Ana Sierra; Ekaterina Subbotina; Mark E Anderson; William A Coetzee; Denice M Hodgson-Zingman; Leonid V Zingman

doi:10.1016/j.bbrc.2011.10.125

Back

Reduction in number of sarcolemmal K ATP channels slows cardiac action potential duration shortening under hypoxia

Journal article

Peer reviewed

Reduction in number of sarcolemmal K ATP channels slows cardiac action potential duration shortening under hypoxia

Zhiyong Zhu, Colin M-L Burnett, Gennadiy Maksymov, Elizabeth Stepniak, Ana Sierra, Ekaterina Subbotina, Mark E Anderson, William A Coetzee, Denice M Hodgson-Zingman and Leonid V Zingman

Biochemical and biophysical research communications, Vol.415(4), pp.637-641

2011

DOI: 10.1016/j.bbrc.2011.10.125

PMID: 22079630

View Online

Abstract

► Sarcolemmal K ATP channels are essential for cardiac resistance to stress. ► K ATP channel activation shortens action potential duration (APD), conserving energy. ► Reduction in cardiac K ATP channels does not alter magnitude of APD shortening. ► Cardiac K ATP channel number defines rate of APD shortening under hypoxia. ► Sarcolemmal K ATP channel expression defines cardiac energetic efficiency. The cardiovascular system operates under demands ranging from conditions of rest to extreme stress. One mechanism of cardiac stress tolerance is action potential duration shortening driven by ATP-sensitive potassium (K ATP) channels. K ATP channel expression has a significant physiologic impact on action potential duration shortening and myocardial energy consumption in response to physiologic heart rate acceleration. However, the effect of reduced channel expression on action potential duration shortening in response to severe metabolic stress is yet to be established. Here, transgenic mice with myocardium-specific expression of a dominant negative K ATP channel subunit were compared with littermate controls. Evaluation of K ATP channel whole cell current and channel number/patch was assessed by patch clamp in isolated ventricular cardiomyocytes. Monophasic action potentials were monitored in retrogradely perfused, isolated hearts during the transition to hypoxic perfusate. An 80–85% reduction in cardiac K ATP channel current density results in a similar magnitude, but significantly slower rate, of shortening of the ventricular action potential duration in response to severe hypoxia, despite no significant difference in coronary flow. Therefore, the number of functional cardiac sarcolemmal K ATP channels is a critical determinant of the rate of adaptation of myocardial membrane excitability, with implications for optimization of cardiac energy consumption and consequent cardioprotection under conditions of severe metabolic stress.

Heart

K ATP

Monophasic action potential

Glyburide

ATP-sensitive potassium channel

Details

Title: Subtitle: Reduction in number of sarcolemmal K ATP channels slows cardiac action potential duration shortening under hypoxia
Creators: Zhiyong Zhu - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Colin M-L Burnett - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Gennadiy Maksymov - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Elizabeth Stepniak - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Ana Sierra - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Ekaterina Subbotina - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Mark E Anderson - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
William A Coetzee - Department of Pediatrics, NYU School of Medicine, New York, NY 10016, USA
Denice M Hodgson-Zingman - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Leonid V Zingman - Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.415(4), pp.637-641
DOI: 10.1016/j.bbrc.2011.10.125
PMID: 22079630
NLM abbreviation: Biochem Biophys Res Commun
ISSN: 0006-291X
eISSN: 1090-2104
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: HL092286, HL093368, HL085820; name: The Carver Trust, award: 01-224; name: The Central Society for Clinical Research; DOI: 10.13039/100002069, name: Fraternal Order of Eagles
Language: English
Date published: 2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984094371602771

Metrics

30 Record Views

18 Times Cited - Web of Science