Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics

Richard J. Gumina, Darko Pucar, Peter Bast, Denice M. Hodgson, Christopher E. Kurtz, Petras P. Dzeja, Takashi Miki, Susumu Seino, Andre Terzic

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118 Scopus citations

Abstract

Although ischemic preconditioning induces bioenergetic tolerance and thereby remodels energy metabolism that is crucial for postischemic recovery of the heart, the molecular components associated with preservation of cellular energy production, transfer, and utilization are not fully understood. Here myocardial bioenergetic dynamics were assessed by 18O-assisted 31P-NMR spectroscopy in control or preconditioned hearts from wild-type (WT) or Kir6.2-knockout (Kir6.2-KO) mice that lack metabolism-sensing sarcolemmal ATP-sensitive K+ (KATP) channels. In WT vs. Kir6.2-KO hearts, preconditioning induced a significantly higher total ATP turnover (232 ± 20 vs. 155 ± 15 nmol·mg protein-1·min-1), ATP synthesis rate (58 ± 3 vs. 46 ± 3% 18O labeling of γ-ATP), and ATP consumption rate (51 ± 4 vs. 31 ± 4% 18O labeling of Pi) after ischemia-reperfusion. Moreover, preconditioning preserved cardiac creatine kinase-catalyzed phosphotransfer in WT (234 ± 26 nmol·mg protein-1·min-1) but not Kir6.2-KO (133 ± 18 nmol·mg protein-1·min-1) hearts. In contrast with WT hearts, preconditioning failed to preserve contractile recovery in Kir6.2-KO hearts, as tight coupling between postischemic performance and high-energy phosphoryl transfer was compromised in the KATP-channel-deficient myocardium. Thus intact KATP channels are integral in ischemic preconditioning-induced protection of cellular energetic dynamics and associated cardiac performance.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number6 53-6
StatePublished - Jun 1 2003

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Keywords

  • ATP-sensitive K channel
  • Cardioprotection
  • Ischemia
  • Metabolism

ASJC Scopus subject areas

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

Cite this

Gumina, R. J., Pucar, D., Bast, P., Hodgson, D. M., Kurtz, C. E., Dzeja, P. P., Miki, T., Seino, S., & Terzic, A. (2003). Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics. American Journal of Physiology - Heart and Circulatory Physiology, 284(6 53-6).