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

ATP敏感性钾(K&lt；ATP&gt；)通道存在于多种组织中，包括血管和膀胱平滑肌。两种类型的成孔亚基Kir6.1和Kir6.2对K&lt；ATP&gt；通道的多样性有贡献。为了确定血管和膀胱平滑肌的工作亚基，我们用Kir6.2缺乏的小鼠研究了K~+通道开放剂(KCOS)、吡那地尔和二氮卓的药理作用。在用去甲肾上腺素预收缩的Kir6.2和Kir6.2^&lt；-/-&gt；(KO)和Kir6.2^&lt；+/+&gt；(WT；)上，吡那地尔和二氮卓产生浓度依赖的松弛效应。吡那地尔还在KO和WT的主动脉平滑肌细胞上诱导了类似幅度的格列本脲敏感电流，并在氨甲酸乙酯麻醉的KO和WT小鼠中诱导了相当水平的低血压。此外，在卡巴胆碱预收缩的KO和WT尿囊中，吡那地尔具有相似的松弛作用。吡那地尔还在Kir6.2和Kir6.2；+/+&gt；膀胱肌细胞上诱导了类似幅度的格列本脲敏感电流，提示Kir6.2在血管组织和膀胱的平滑肌细胞中没有重要作用。

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.