Panaghie Gianina, Abbott Geoffrey W
Greenberg Division of Cardiology, Department of Medicine, Cornell University, Weill Medical College, 520 East 70th Street, New York, NY 10021, USA.
Curr Pharm Des. 2006;12(18):2285-302. doi: 10.2174/138161206777585175.
Voltage-gated potassium channels (Kv channels) are the major determinants of cellular repolarization in excitable cells--they open in response to depolarization and facilitate selective efflux of potassium ions across the plasma membrane. Because of the importance of exquisitely timed cellular repolarization in controlling action potential morphology and duration, Kv channels are attractive therapeutic targets, particularly for drugs aimed at controlling aberrant electrical excitability such as is observed in cardiac arrhythmia and epilepsy. While the pore-forming alpha subunits of Kv channels are sufficient to form functional channels, a host of cytoplasmic and transmembrane ancillary subunits modulate their trafficking, function and regulation in vivo. Here, we consider the impact of ancillary subunits on Kv channel pharmacology, and discuss how increased understanding of the roles of ancillary subunits in native Kv channel complexes will lead to development of safer, more specific and more efficacious therapeutic small molecules.
电压门控钾通道（Kv通道）是可兴奋细胞中细胞复极化的主要决定因素——它们在去极化时开放，并促进钾离子选择性地跨质膜外流。由于精确计时的细胞复极化在控制动作电位形态和持续时间方面至关重要，Kv通道是有吸引力的治疗靶点，特别是对于旨在控制异常电兴奋性的药物，如在心律失常和癫痫中观察到的情况。虽然Kv通道的孔形成α亚基足以形成功能性通道，但许多细胞质和跨膜辅助亚基在体内调节它们的运输、功能和调控。在这里，我们考虑辅助亚基对Kv通道药理学的影响，并讨论对辅助亚基在天然Kv通道复合物中作用的更多了解将如何导致更安全、更特异和更有效的治疗性小分子的开发。
