title: Mitochondrial KATP channel-dependent and -independent phases of ischemic preconditioning against myocardial infarction in the rat.
abstract: To obtain insight into the role of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel in ischemic preconditioning (PC), we aimed to clarify the mitoK(ATP) channel-dependent phase of PC in two PC protocols with different intervals between PC ischemia and an index ischemia. The possible contribution of mitoK(ATP) channel opening to protein kinase C activation in PC was also examined by Western blotting. Myocardial infarction was induced by 30-min coronary occlusion/2-h reperfusion in rat hearts in situ, and infarct size was expressed as a percentage of the area at risk (% IS/AR). PC was performed with 2 episodes of 5-min ischemia, and each heart was subjected to 30-min ischemia either 5 min or 20 min after PC. At 5 min after PC, both PKC-delta and -epsilon were translocated and the myocardium was protected against infarction (% IS/AR = 28.3 +/- 2.7 % vs. 72.7 +/- 2.2 in controls p < 0.05). Pretreatment with a selective mitoK(ATP) channel blocker, 5-hydroxydecanoate (5-HD, 10 mg/kg), abolished the cardioprotection but not PKC translocation by PC. At 20 min after PC, PKC translocation remained at the same level as that 5 min after PC, but the anti-infarct tolerance was attenuated (%IS/AR = 43.5 +/- 4.7 %). Injection of 5-HD after PC did not affect anti-infarct tolerance at 5 min after PC but abolished the protection at 20 min after PC without any effects on PKC. These results suggest that the mitoK(ATP) channel plays a role in triggering of PC in a PKC-independent manner and that the role of the mitoK(ATP) channel as a mediator of protection is detectable after, but not before, the PC effect starts to decay without a change in the level of PKC translocation in the rat heart.
authors.affiliation: Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Japan.
authors.forename: Yukinaga
authors.initials: Y
authors.lastname: Nozawa
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ohnuma
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yano
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D004195:Disease Models, Animal; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D019194:Ischemic Preconditioning; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D009929:Organ Size; D010316:Particle Size; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D011493:Protein Kinase C