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ATP敏感钾通道(ATP-sensitive potassium channel, KATP通道)广泛分布在血管系统,并在血管张力调节中发挥重要作用。 KATP通道由4个孔道形成的内向整流钾离子通道(inward rectifier K+ channels, Kir)亚基和4个磺脲受体调节亚基(sulfonylu-rea receptor, SUR)组成。尽管其它一些亚基在血管中也存在,Kir6.1/SUR2B是主要的血管亚型KATP通道。KATP通道转基因小鼠的研究以及人群中KATP通道基因突变的发现,都强烈支持KATP通道对于心血管系统的动态平衡调控是不可缺少的。大量的血管活性物质通过调节KATP通道活性来改变血管平滑肌细胞的膜电位,从而调节血管张力。多数内源性血管收缩物质,例如血管加压素,激活蛋白激酶C (protein kinase C, PKC),磷酸化KATP通道并抑制其活性;而血管扩张物质,如血管活性肠肽,通过增加cAMP的形成和提高蛋白激酶A (protein kinase A, PKA)的活性来增加KATP通道的活性。PKC作用于Kir6.1亚基C-末端,磷酸化4个保守的丝氨酸,而PKA磷酸化SUR2B亚基第2核苷酸结合域的Ser1387位点。血管KATP通道也受活性氧的调节,其中Kir6.1的Cys176是一个重要的过氧化物调节位点。此外,KATP通道功能可被一些慢性的病理生理条件上调,如感染性休克。核因子-κB依赖的基因转录是脂多糖诱导的血管KATP通道激活的一个机制。本综述将概括性描述血管KATP通道在生理和病理情况下受到的调节,以期阐明血管KATP通道在治疗和预防心血管疾病方面可能是一个有用的靶点。
ATP-sensitive potassium channels (KATP channels) are widely distributed in the vascular system and play an important role in the regulation of vascular tone. The KATP channel consists of four rectifier channels (inward rectifier K + channels, Kir) and four sulfonylulate receptor (SUR). Kir6.1 / SUR2B is the major vascular subtype KATP channel, although some other subunits are also present in blood vessels. The study of KATP channel transgenic mice and the discovery of KATP channel mutations in the population strongly support that KATP channels are indispensable for the regulation of cardiovascular homeostasis. A large number of vasoactive substances regulate vascular tone by altering the membrane potential of vascular smooth muscle cells by modulating KATP channel activity. Most endogenous vasoconstrictors, such as vasopressin, activate protein kinase C (PKC), phosphorylate KATP channels and inhibit their activity; whereas vasodilators, such as vasoactive intestinal peptide, act by increasing cAMP The formation and increase of protein kinase A (PKA) activity to increase KATP channel activity. PKC acts on the C-terminus of the Kir6.1 subunit, phosphorylates 4 conserved serines, and PKA phosphorylates the Ser1387 site of the 2nd nucleotide binding domain of the SUR2B subunit. Vascular KATP channels are also regulated by reactive oxygen species, of which Kir6.1 Cys176 is an important peroxide regulatory site. In addition, KATP channel function can be up-regulated by a number of chronic pathophysiological conditions, such as septic shock. Nuclear factor-κB-dependent gene transcription is a mechanism of lipopolysaccharide-induced activation of vascular KATP channels. This review summarizes the regulation of vascular KATP channels under physiological and pathological conditions to clarify that vascular KATP channels may be a useful target for the treatment and prevention of cardiovascular disease.