Faculty Collaboration Database

Ischemic preconditioning in rats: role of mitochondrial K(ATP) channel in preservation of mitochondrial function. Am J Physiol Heart Circ Physiol 2000 Jan;278(1):H305-12

Date

01/25/2000

Pubmed ID

10644614

DOI

10.1152/ajpheart.2000.278.1.H305

Scopus ID

2-s2.0-0033955679 (requires institutional sign-in at Scopus site)   239 Citations

Abstract

We examined the role of the sarcolemmal and mitochondrial K(ATP) channels in a rat model of ischemic preconditioning (IPC). Infarct size was expressed as a percentage of the area at risk (IS/AAR). IPC significantly reduced infarct size (7 +/- 1%) versus control (56 +/- 1%). The sarcolemmal K(ATP) channel-selective antagonist HMR-1098 administered before IPC did not significantly attenuate cardioprotection. However, pretreatment with the mitochondrial K(ATP) channel-selective antagonist 5-hydroxydecanoic acid (5-HD) 5 min before IPC partially abolished cardioprotection (40 +/- 1%). Diazoxide (10 mg/kg iv) also reduced IS/AAR (36.2 +/- 4.8%), but this effect was abolished by 5-HD. As an index of mitochondrial bioenergetic function, the rate of ATP synthesis in the AAR was examined. Untreated animals synthesized ATP at 2.12 +/- 0.30 micromol x min(-1) x mg mitochondrial protein(-1). Rats subjected to ischemia-reperfusion synthesized ATP at 0.67 +/- 0.06 micromol x min(-1) x mg mitochondrial protein(-1). IPC significantly increased ATP synthesis to 1.86 +/- 0.23 micromol x min(-1) x mg mitochondrial protein(-1). However, when 5-HD was administered before IPC, the preservation of ATP synthesis was attenuated (1.18 +/- 0.15 micromol x min(-1) x mg mitochondrial protein(-1)). These data are consistent with the notion that inhibition of mitochondrial K(ATP) channels attenuates IPC by reducing IPC-induced protection of mitochondrial function.

Author List

Fryer RM, Eells JT, Hsu AK, Henry MM, Gross GJ

Author

Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Decanoic Acids
Diazoxide
Hemodynamics
Hydroxy Acids
Ischemic Preconditioning, Myocardial
Male
Membrane Proteins
Mitochondria, Heart
Myocardial Infarction
Myocardium
Osmolar Concentration
Potassium Channels
Rats
Rats, Wistar