Mitochondrial K ATP 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.

The Tyrosine Phosphatase Inhibitor Bis(Maltolato)Oxovanadium Attenuates Myocardial Reperfusion Injury by Opening ATP-Sensitive Potassium Channels

“…Another mechanism by which an increase in tyrosine phosphorylation may exert cardioprotection could involve opening of K ϩ ATP channels, which is suggested by studies showing that ischemic preconditioning involves activation of tyrosine kinase and protein kinase C (Vahlhaus et al, 1998;Fryer et al, 1999) and opening of K ϩ ATP channels (Schultz et al, 1997). Although the sequence of involvement is still controversial (Pain et al, 2000), studies in the rat heart suggest that kinases are principally involved early in preconditioning and act upstream of the K ϩ ATP channels (Fryer et al, 1999(Fryer et al, , 2001Nozawa et al, 2003). In accordance with this concept, we observed that the K ϩ ATP channel blocker glibenclamide, which had no effect on infarct size per se, abolished the cardioprotection by BMOV, suggesting that opening of K ϩ ATP channels is involved in the actions of BMOV.…”

Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3β

“…Surgical preparation was essentially the same as in our previous studies using rats (31,37). In brief, male Sprague-Dawley rats weighing 260 -350 g were anesthetized with pentobarbital sodium (40 mg/kg ip), intubated, and mechanically ventilated with a Harvard Respirator (model 683, Harvard Apparatus, South Natick, MA).…”

KATP channels and myocardial preconditioning: an update

“…In addition, whereas infusion of diazoxide leads to a marked reduction in infarct size, diazoxide treatment failed to translocate PKC-⑀ or accelerate its translocation. More recently, Nozawa et al (36) showed that IPC in rats produced a translocation of both PKC-␦ and PKC-⑀; however, 5-HD blocked the effect of IPC without blocking the translocation of the two PKC isoforms. These results suggest that the mito K ATP channel or site of action of 5-HD is distal to PKC.…”