Mice lacking sulfonylurea receptor 2 (SUR2) ATP-sensitive potassium channels are resistant to acute cardiovascular stress

Douglas Stoller, Rahul Kakkar, Matthew Smelley, Karel Chalupsky, Judy U. Earley, Nian Qing Shi, Jonathan C. Makielski, Elizabeth M. McNally

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Adenosine triphosphate-sensitive potassium (KATP) channels are thought to mediate the stress response by sensing intracellular ATP concentration. Cardiomyocyte KATP channels are composed of the pore-forming Kir6.2 subunit and the regulatory sulfonylurea receptor 2 (SUR2). We studied the response to acute isoproterenol in SUR2 null mice as a model of acute adrenergic stress and found that the episodic coronary vasospasm observed at baseline in SUR2 null mice was alleviated. Similar results were observed following administration of a nitric oxide donor consistent with a vasodilatory role. Langendorff-perfused hearts were subjected to global ischemia, and hearts from SUR2 null mice exhibited significantly reduced infarct size (54 ± 4 versus 30 ± 3%) and improved cardiac function compared to control mice. SUR2 null mice have hypertension and develop cardiac hypertrophy. However, despite longstanding hypertension, fibrosis was absent in SUR2 null mice. SUR2 null mice were administered nifedipine to block baseline coronary vasospasm, and hearts from nifedipine-treated SUR2 null mice exhibited increased infarct size compared to untreated SUR2 null mice (42 ± 3% versus 54 ± 3%). We conclude that conventional sarcolemmal cardiomyocyte KATP channels containing full-length SUR2 are not required for mediating the response to acute cardiovascular stress.

Original languageEnglish (US)
Pages (from-to)445-454
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume43
Issue number4
DOIs
StatePublished - Oct 1 2007

Keywords

  • Cardiac stress
  • K channel
  • Myocardial infarction
  • Sulfonylurea receptor
  • Vasospasm

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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