AIM: To test whether ischemic preconditioning (IPC) del ays ischemia-induced electrical uncoupling by activation of mitochondrial ATP-se nsitive potassium channels (mitoK ATP ). METHODS: Adult rat hearts perfused on a Langendorf f apparatus were subjected to 40 min ischemia followed by 30 min reperfusion. C han ges in coupling were monitored by measuring whole-tissue resistance. RES ULTS: IP C delayed the onset of uncoupling campared to ischemic control; Blocking mitoK ATP channels before the IPC protocol abolished the delay of uncoupling. The specif ic mitoK ATP channel opener diazoxide mimicked the protective effect of IPC . The delay induced by diazoxide was reduced by 5-HD, L-type Ca 2+ channel inhibitor verapamil and a free radical scavenger N-(2-mercaptopropionyl)glycine. CONCLUSIONS: IPC delays the onset of cellular electrical uncoup ling induced by acute ischemia, in which activation of the mitoK ATP channe ls may be involved.