A role of opening of mitochondrial ATP-sensitive potassium channels in the infarct size-limiting effect of ischemic preconditioning via activation of protein kinase C in the canine heart.
The opening of mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels triggers or mediates the infarct size (IS)-limiting effect of ischemic preconditioning (IP). Because ecto-5'-nucleotidase related to IP is activated by PKC, we tested whether the opening of mitoK(ATP) channels activates PKC and contributes to either activation of ecto-5'-nucleotidase or IS-limiting effect. In dogs, IP procedure decreased IS and activated ecto-5'-nucleotidase, both of which were mimicked by transient exposure to either cromakalim or diazoxide, and these effects were blunted by either GF109203X (a PKC inhibitor) or 5-hydroxydecanoate (a mitoK(ATP) channel blocker), but not by HMR-1098 (a surface sarcolenmal K(ATP) channel blocker). Either cromakalim or diazoxide activated both PKC and ecto-5'-nucleotidase, which was blunted by either GF109203X or 5-hydroxydecanoate, but not by HMR-1098. We concluded that the opening of mitoK(ATP) channels contributes to either activation of ecto-5'-nucleotidase or the infarct size-limiting effect via activation of PKC in canine hearts.
Tsukamoto
Osamu
O
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
Asanuma
Hiroshi
H
Kim
Jiyonng
J
Minamino
Tetsuo
T
Takashima
Seiji
S
Ogai
Akiko
A
Hirata
Akio
A
Fujita
Masashi
M
Shinozaki
Yoshiro
Y
Mori
Hidezo
H
Tomoike
Hitonobu
H
Hori
Masatsugu
M
Kitakaze
Masafumi
M
D015720:5'-Nucleotidase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology; D003652:Decanoic Acids / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006880:Hydroxy Acids / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D019194:Ischemic Preconditioning; D008301:Maleimides / Q000008:administration & dosage / Q000494:pharmacology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*
D001549:Benzamides; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007211:Indoles; D008301:Maleimides; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; C410297:HMR 1098; D011493:Protein Kinase C; D015720:5'-Nucleotidase; C070515:bisindolylmaleimide I