Functional roles of vascular ATP-sensitive potassium channels clarified by Kir6.2-knockout mice.

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ATP-sensitive potassium (K_<ATP>) channels have been found in numerous tissues including vascular and urinary bladder smooth muscles. Two types of the pore-forming subunits, Kir6.1 and Kir6.2, contribute to the diversity of K_<ATP> channels. To determine operative subunits in the vascular and urinary bladder smooth muscles, we characterized the pharmacological effects of K^+ channel openers (KCOs), pinacidil and diazoxide, using Kir6.2-deficient mice.Pinacidil and diazoxide produced concentration-dependent relaxing effects in the Kir6.2^<-/-> (KO) and Kir6.2^<+/+> (WT) aortas precontracted with norepinephrine. Pinacidil also induced a glibenclamide-sensitive current of similar magnitude in both KO and WT aortic smooth muscle cells, and compalable levels of hypotension in urethaneanesthetized KO and WT mice. In addition, pinacidil produced the relaxing effects with similar potency in both KO and WT urinary bladders precontracted with carbachol. Pinacidil also induced a glibenclamide-sensitive current of similar magnitude in both Kir6.2^<-/-> and Kir6.2^<+/+> bladders.Theses findings indicated that the Kir6.2 plays no important role in the smooth muscle cells of vascular tissues and urinary bladder.