Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 284, Issue 6, Pages H2106-H2113Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00057.2003
Keywords
ATP-sensitive K+ channel; cardioprotection; ischemia; metabolism
Funding
- NHLBI NIH HHS [HL-64822, HL-07111] Funding Source: Medline
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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 O-18-assisted P-31-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+ (K-ATP) 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% O-18 labeling of gamma-ATP), and ATP consumption rate (51 +/- 4 vs. 31 +/- 4% O-18 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 K-ATP-channel-deficient myocardium. Thus intact K-ATP channels are integral in ischemic preconditioning-induced protection of cellular energetic dynamics and associated cardiac performance.
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