Cardiomyocyte sulfonylurea receptor 2-K ATP channel mediates cardioprotection and ST segment elevation

Douglas A. Stoller, John P. Fahrenbach, Karel Chalupsky, Bi Hua Tan, Nitin Aggarwal, Jamie Metcalfe, Michele Hadhazy, Nian Qing Shi, Jonathan C. Makielski, Elizabeth M. McNally

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Sulfonylurea receptor-containing ATP-sensitive potassium (K ATP) channels have been implicated in cardioprotection, but the cell type and constitution of channels responsible for this protection have not been clear. Mice deleted for the first nucleotide binding region of sulfonylurea receptor 2 (SUR2) are referred to as SUR2 null since they lack full-length SUR2 and glibenclamide-responsive K ATP channels in cardiac, skeletal, and smooth muscle. As previously reported, SUR2 null mice develop electrocardiographic changes of ST segment elevation that were shown to correlate with coronary artery vasospasm. Here we restored expression of the cardiomyocyte SUR2-K ATP channel in SUR2 null mice by generating transgenic mice with ventricular cardiomyocyte-restricted expression of SUR2A. Introduction of the cardiomyocyte SUR2A transgene into the SUR2 null background restored functional cardiac K ATP channels. Hearts isolated from rescued mice, referred to as MLC2A, had significantly reduced infarct size (27 ± 3% of area at risk) compared with SUR2 null mice (36 ± 3% of area at risk). Compared with SUR2 null hearts, MLC2A hearts exhibited significantly improved cardiac function during the postischemia reperfusion period primarily because of preservation of low diastolic pressures. Additionally, restoration of cardiac SUR2-K ATP channels significantly reduced the degree and frequency of ST segment elevation episodes in MLC2A mice. Therefore, cardioprotective mechanisms both dependent and independent of SUR2-K ATP channels contribute to cardiac function.

Original languageEnglish (US)
Pages (from-to)H1100-H1108
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume299
Issue number4
DOIs
StatePublished - Oct 2010

Keywords

  • ATP-sensitive potassium channel
  • Ischemia
  • SUR2
  • SUR2A
  • Vasospasm

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Stoller, D. A., Fahrenbach, J. P., Chalupsky, K., Tan, B. H., Aggarwal, N., Metcalfe, J., Hadhazy, M., Shi, N. Q., Makielski, J. C., & McNally, E. M. (2010). Cardiomyocyte sulfonylurea receptor 2-K ATP channel mediates cardioprotection and ST segment elevation. American Journal of Physiology - Heart and Circulatory Physiology, 299(4), H1100-H1108. https://doi.org/10.1152/ajpheart.00084.2010