Activation of mitochondrial ATP-sensitive potassium channels delays ischemia-induced cellular uncoupling in rat heart.
OBJECTIVE
To test the hypothesis that cellular uncoupling induced by myocardial ischemia is mediated by activation of mitochondrial ATP-sensitive potassium channels (mitoKATP).


METHODS
Rat hearts were perfused on a Langendorff apparatus and subjected to 40-min ischemia followed by 30-min reperfusion (I/R). Changes in cellular coupling were monitored by measuring whole-tissue resistance.


RESULTS
(1) In hearts subjected to I/R, the onset of uncoupling started at (13.3+/-1.0) min of ischemia; (2) Ischemic preconditioning (IPC) delayed the onset of uncoupling until (22.7+/-1.3) min. Blocking mitoKATP channels with 5-hydroxydecanoate (5-HD) before the IPC abolished the uncoupling delay [(12.6+/-1.6) min]; (3) Calcium preconditioning (CPC) had the same effect as IPC. And this effect was reversed by blocking the mitoKATP channel again. In the CPC group the onset of uncoupling occurred after (20.6+/-1.3) min, and this was canceled by 5-HD [(13.6+/-0.8) min]; (4) In hearts pretreated with the specific mitoKATP channel opener diazoxide before sustained ischemia, the onset was delayed to (18.4+/-1.4) min; (5) 5-HD canceled the protective effects of diazoxide (12.6+/-1.0) min; and both the L-type Ca2+ channel inhibitor verapamil and the free radical scavenger N-(2-mercaptopropionyl)glycine, reduced the extended onset time induced by diazoxide [to (13.3+/-1.8) min and (13.4+/-2.1) min, respectively].


CONCLUSIONS
IPC and CPC delay the onset of cellular uncoupling induced by acute ischemia in rat heart, and the underlying mechanism involves activation of the mitoKATP channels.
Shen
Yue-Liang
YL
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031, China. xiaqiang@zju.edu.cn
Chen
Ying-Ying
YY
Wu
Xun-Dong
XD
Bruce
Iain C
IC
Xia
Qiang
Q
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D014700:Verapamil; D003981:Diazoxide