Opening of Ca2+-activated K+ channels is involved in ischemic preconditioning in canine hearts.
Brief periods of ischemia that precede sustained ischemia can markedly reduce infarct size (IS), a phenomenon that is known as ischemic preconditioning (IP). Several investigators have shown that elevation of the intracellular Ca(2+) level ([Ca(2+)](i)) during the antecedent brief periods of ischemia triggers the cardioprotective mechanism of IP. Since opening of Ca(2+) activated K(+) (K(Ca)) channels is reported to be cardioprotective, we hypothesized that these channels may be involved in the cardioprotective mechanism of IP. In anesthetized open-chest dogs, myocardial ischemia/reperfusion injury was created by occlusion of the left anterior descending coronary artery (LAD) for 90 min followed by 6 h of reperfusion. First, we showed that the treatment with NS1619, a K(Ca) channel opener, reduced IS (IS in NS1619 group and control group, 19.8 +/- 5.5% vs. 45.4 +/- 3.5% of the area at risk, P < 0.05). Next, four cycles coronary occlusion for 5 min and reperfusion (IP) were performed before the 90-min occlusion with or without the infusion of potent K(Ca) channel inhibitors, iberiotoxin (IbTX) and charybdotoxin (ChTX). IP markedly reduced IS (IS in the IP group was 8.2 +/- 1.8%, P < 0.01 vs. control group). Infusion of either of K(Ca) channel blockers during IP blunted the IS-limiting effect of IP (IS in the IP + IbTX and IP + ChTX groups was 30.7 +/- 7.0% and 35.5 +/- 3.7%, respectively, P < 0.05, vs. IP group). However, the cardioprotective effect of IP was not blunted by the treatment with ChTX when treated only during reperfusion (14.0 +/- 4.1%). Thus, we conclude that the opening of K(Ca) channel is involved in early trigger phase of the molecular mechanism of IP.
Shintani
Yasunori
Y
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
Node
Koichi
K
Asanuma
Hiroshi
H
Sanada
Shoji
S
Takashima
Seiji
S
Asano
Yoshihiro
Y
Liao
Yulin
Y
Fujita
Masashi
M
Hirata
Akio
A
Shinozaki
Yoshiro
Y
Fukushima
Tomi
T
Nagamachi
Yoko
Y
Okuda
Hiroko
H
Kim
Jiyoong
J
Tomoike
Hitonobu
H
Hori
Masatsugu
M
Kitakaze
Masafumi
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism*
D024681:Potassium Channels, Calcium-Activated; D002118:Calcium