Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Curr Med Chem. 2012;19(9):1405-20. doi: 10.2174/092986712799462595.
The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).
缓慢延迟整流电流(I(Ks)))是心脏延迟整流电流的缓慢成分,对心脏动作电位的晚期复极至关重要。该电流也是交感神经系统(SNS)调节心脏电活动以适应运动或情绪应激引起的心率变化的重要靶点,并可被β-肾上腺素能或其他信号分子上调。I(Ks) 通道由形成孔的 KCNQ1α亚基和辅助 KCNE1β亚基的共组装产生。任何亚基的突变都会导致严重的长 QT 综合征(LQT-1、LQT-5),其特征是晕厥、癫痫发作和猝死。本综述总结了 I(Ks) 通道的正常生理功能和分子基础,并说明了其阻滞剂和激动剂的最新发展。因此,目前的广泛研究应该有助于深入了解 I(Ks) 通道在调节心脏功能中的作用,并为 I(Ks) 通道阻滞剂和激动剂作为潜在的抗心律失常药物或药理学工具的发展提供一些指导,以确定 I(Ks) 的生理和病理功能。