Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Acta Pharmacol Sin. 2018 May;39(5):683-694. doi: 10.1038/aps.2018.10. Epub 2018 Apr 19.
ATP-sensitive potassium (K) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. K channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. K channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone. Under pathophysiological conditions, K channels play cytoprotective role in cardiac myocytes and neurons during ischemia and/or hypoxia. K channel is a hetero-octameric complex, consisting of four pore-forming Kir6.x and four regulatory sulfonylurea receptor SURx subunits. These subunits are differentially expressed in various cell types, thus determining the sensitivity of the cells to specific channel modifiers. Sulfonylurea class of antidiabetic drugs blocks K channels, which are neuroprotective in stroke, can be one of the high stoke risk factors for diabetic patients. In this review, we discussed the potential effects of K channel blockers when used under pathological conditions related to diabetics and cerebral ischemic stroke.
三磷酸腺苷敏感性钾 (K) 通道广泛表达于多种器官的细胞膜上,包括心脏、胰腺和大脑。K 通道在控制和调节细胞功能方面发挥着重要作用,其活性受到代谢状态的影响,可被 ATP 抑制,被 Mg-ADP 激活,使细胞能够将细胞代谢状态(ATP/ADP 比值)与细胞膜的电活动偶联。K 通道介导胰岛β细胞中的胰岛素分泌,并调节血管张力。在病理生理条件下,K 通道在心梗和/或缺氧期间在心肌细胞和神经元中发挥细胞保护作用。K 通道是一种异源八聚体复合物,由四个孔形成的 Kir6.x 和四个调节磺酰脲受体 SURx 亚基组成。这些亚基在不同的细胞类型中表达不同,从而决定了细胞对特定通道调节剂的敏感性。磺酰脲类降糖药物可阻断 K 通道,在中风中具有神经保护作用,可能是糖尿病患者中风风险高的因素之一。在这篇综述中,我们讨论了 K 通道阻滞剂在与糖尿病和脑缺血性中风相关的病理条件下使用时的潜在影响。