Faculty Collaboration Database

KATP channel openers have opposite effects on mitochondrial respiration under different energetic conditions. J Cardiovasc Pharmacol 2008 May;51(5):483-91

Date

04/26/2008

Pubmed ID

18437094

Pubmed Central ID

PMC3010203

DOI

10.1097/FJC.0b013e31816bf4a4

Scopus ID

2-s2.0-41349099062 (requires institutional sign-in at Scopus site)   54 Citations

Abstract

Mitochondrial (m) KATP channel opening has been implicated in triggering cardiac preconditioning. Its consequence on mitochondrial respiration, however, remains unclear. We investigated the effects of two different KATP channel openers and antagonists on mitochondrial respiration under two different energetic conditions. Oxygen consumption was measured for complex I (pyruvate/malate) or complex II (succinate with rotenone) substrates in mitochondria from fresh guinea pig hearts. One of two mKATP channel openers, pinacidil or diazoxide, was given before adenosine diphosphate in the absence or presence of an mKATP channel antagonist, glibenclamide or 5-hydroxydecanoate. Without ATP synthase inhibition, both mKATP channel openers differentially attenuated mitochondrial respiration. Neither mKATP channel antagonist abolished these effects. When ATP synthase was inhibited by oligomycin to decrease [ATP], both mKATP channel openers accelerated respiration for both substrate groups. This was abolished by mKATP channel blockade. Thus, under energetically more physiological conditions, the main effect of mKATP channel openers on mitochondrial respiration is differential inhibition independent of mKATP channel opening. In contrast, under energetically less physiological conditions, mKATP channel opening can be evidenced by accelerated respiration and blockade by antagonists. Therefore, the effects of mKATP channel openers on mitochondrial function likely depend on the experimental conditions and the cell's underlying energetic state.

Author List

Riess ML, Camara AK, Heinen A, Eells JT, Henry MM, Stowe DF

Authors

Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of Wisconsin
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

Animals
Decanoic Acids
Diazoxide
Electron Transport Complex I
Electron Transport Complex II
Glyburide
Guinea Pigs
Hydroxy Acids
In Vitro Techniques
Mitochondria, Heart
Mitochondrial Proton-Translocating ATPases
Oxygen Consumption
Pinacidil
Potassium Channel Blockers
Potassium Channels