Document Type

Article

Language

eng

Format of Original

9 p.

Publication Date

5-2008

Publisher

Lippincott Williams & Wilkins, Inc.

Source Publication

Journal of Cardiovascular Pharmacology

Source ISSN

0160-2446

Original Item ID

doi: 10.1097/FJC.0b013e31816bf4a4

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.

Comments

Accepted version. Journal of Cardiovascular Pharmacology, Vol. 51, No. 5 (May 2008): 483-491. DOI. © Lippincott Williams & Wilkins, Inc. 2008. Used with permission.

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