title: KATP channel openers have opposite effects on mitochondrial respiration under different energetic conditions.
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.
authors.affiliation: Anesthesiology Research Laboratories, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. mriess@mcw.edu
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Riess
authors.forename: Amadou K S
authors.initials: AK
authors.lastname: Camara
authors.forename: André
authors.initials: A
authors.lastname: Heinen
authors.forename: Janis T
authors.initials: JT
authors.lastname: Eells
authors.forename: Michele M
authors.initials: MM
authors.lastname: Henry
authors.forename: David F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000378:metabolism / Q000494:pharmacology*; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects*; D020110:Pinacidil / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000819:agonists*
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; D042963:Electron Transport Complex II; D025261:Mitochondrial Proton-Translocating ATPases; D042967:Electron Transport Complex I; D003981:Diazoxide; D005905:Glyburide