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Role of mitochondrial K ATP channels and protein kinase C in ischaemic preconditioning
Author(s) -
Uchiyama Yuka,
Otani Hajime,
Wakeno Mayu,
Okada Takayuki,
Uchiyama Takamichi,
Sumida Tomohiko,
Kido Masakuni,
Imamura Hiroji,
Nakao Shinichi,
Shingu Koh
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03853.x
Subject(s) - cardioprotection , chelerythrine , protein kinase c , diazoxide , pharmacology , chemistry , flavoprotein , ischemia , rottlerin , ischemic preconditioning , biochemistry , medicine , kinase , enzyme , insulin
Summary 1. Activation of mitochondrial K ATP (mitoK ATP ) channels and protein kinase C (PKC) has been implicated in cardioprotective mechanisms of ischaemic preconditioning (IPC). However, the exact role of these events in early IPC remains unclear. 2. Isolated and perfused rat hearts underwent IPC with three cycles of 5 min ischaemia and 5 min reperfusion. The heart was subjected to 30 min global ischaemia followed by 120 min reperfusion. Flavoprotein oxidation was monitored to assess mitoK ATP channel activity. Cardioprotection was evaluated by recovery of isovolumic left ventricular (LV) function and infarct size. 3. Diazoxide (50 mgr;mol/L) increased flavoprotein oxidation and conferred cardioprotection in a manner sensitive to the selective mitoK ATP channel blocker 5‐hydroxydecanoate (5‐HD; 0.5 mmol/L). 4. Pretreatment with 0.5 mmol/L 5‐HD abrogated IPC‐induced flavoprotein oxidation and cardioprotection, whereas late treatment with 5‐HD after IPC required a higher dose (2 mmol/L) to abolish flavoprotein oxidation and cardioprotection afforded by IPC. 5. Pretreatment with the PKC inhibitors Ro318425 (1 µmol/L) and chelerythrine (5 µmol/L) abolished IPC‐induced flavoprotein oxidation and cardioprotection, whereas late treatment with Ro318425 required a higher dose (4 µmol/L) to abolish flavoprotein oxidation and cardioprotection. 6. In conclusion, these results suggest that activation of mitoK ATP channels is the trigger and the mediator of IPC and that PKC plays a crucial role in both phases of mitoK ATP channel activation, although mitoK ATP channels and PKC may be more activated during the mediator phase.