Contractility and ischemic response of hearts from transgenic mice with altered sarcolemmal KATP channels

R. Rajashree, J. C. Koster, K. P. Markova, C. G. Nichols, P. A. Hofmann

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

The functional significance of ATP-sensitive K+ (KATP) channels is controversial. In the present study, transgenic mice expressing a mutant Kir6.2, with reduced ATP sensitivity, were used to examine the role of sarcolemmal KATP in normal cardiac function and after an ischemic or metabolic challenge. We found left ventricular developed pressure (LVDP) was 15-20% higher in hearts from transgenics in the absence of cardiac hypertrophy. β-Adrenergic stimulation caused a positive inotropic response from nontransgenic hearts that was not observed in transgenic hearts. Decreasing extracellular Ca2+ decreased LVDP in hearts from nontransgenics but not in those from transgenics. These data suggest an increase in intracellular [Ca2+] in transgenic hearts. Additional studies have demonstrated hearts from nontransgenics and transgenics have a similar postischemic LVDP. However, ischemic preconditioning does not improve postischemic recovery in transgenics. Transgenic hearts also demonstrate a poor recovery after metabolic inhibition. These data are consistent with the hypothesis that sarcolemmal KATP channels are required for development of normal myocardial function, and perturbations of KATP channels lead to hearts that respond poorly to ischemic or metabolic challenges.

Original languageEnglish
Pages (from-to)H584-H590
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number2 52-2
DOIs
StatePublished - 2002

Keywords

  • Diastolic pressure
  • Heart rate
  • Ischemic preconditioning
  • Kir6.2
  • Left ventricular developed pressure
  • Metabolic inhibition

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