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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)637-641
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume415
Issue number4
DOIs
StatePublished - Dec 2 2011
Externally publishedYes

Keywords

  • ATP-sensitive potassium channel
  • Glyburide
  • Heart
  • K
  • Monophasic action potential

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Zhu, Z., Burnett, C. M. L., Maksymov, G., Stepniak, E., Sierra, A., Subbotina, E., Anderson, M. E., Coetzee, W. A., Hodgson-Zingman, D. M., & Zingman, L. V. (2011). Reduction in number of sarcolemmal K ATP channels slows cardiac action potential duration shortening under hypoxia. Biochemical and Biophysical Research Communications, 415(4), 637-641. https://doi.org/10.1016/j.bbrc.2011.10.125