MitoK(ATP)-dependent changes in mitochondrial volume and in complex II activity during ischemic and pharmacological preconditioning of Langendorff-perfused rat heart.
It has been proposed that activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is part of signaling pathways triggering the cardioprotection afforded by ischemic preconditioning of the heart. This work was to analyze the mitochondrial function profile of Langendorff-perfused rat hearts during the different phases of various ischemia-reperfusion protocols. Specifically, skinned fibers of ischemic preconditioned hearts exhibit a decline in the succinate-supported respiration and complex II activity during ischemia, followed by a recovery during reperfusion. Meanwhile, the apparent affinity of respiration for ADP (which reflects the matrix volume expansion) is increased during preconditioning stimulus and, to a larger extent, during prolonged ischemia. This evolution pattern is mimicked by diazoxide and abolished by 5-hydroxydecanoate. It is concluded that opening the mitoK(ATP) channel mediates the preservation of mitochondrial structure-function via a mitochondrial matrix shrinkage and a reversible inactivation of complex II during prolonged ischemic insult.
Pasdois
Philippe
P
Inserm U441, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Beauvoit
Bertrand
B
Tariosse
Liliane
L
Vinassa
Béatrice
B
Bonoron-Adèle
Simone
S
Santos
Pierre Dos
PD
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D019069:Cell Respiration / Q000502:physiology; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D042963:Electron Transport Complex II / Q000502:physiology*; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology*; D053142:Mitochondrial Size; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009210:Myofibrils / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019802:Succinic Acid / Q000378:metabolism
D000959:Antihypertensive Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D000244:Adenosine Diphosphate; C052853:5-hydroxydecanoic acid; D019802:Succinic Acid; D042963:Electron Transport Complex II; D003981:Diazoxide