Endocytic regulation of voltage-dependent potassium channels in the heart

Understanding the regulation of cardiac ion channels is critical for the prevention of arrhythmia caused by abnormal excitability. ion channels can be regulated by a change in function (qualitative) and a change in number (quantitative). functional changes have been extensively investigated for many ion channels including cardiac voltage-dependent potassium channels. by contrast,the regulation of ion channel numbers has not been widely examined,particularly with respect to acute modulation of ion channels. this article briefly summarizes stimulus-induced endocytic regulation of major voltage-dependent potassium channels in the heart. the stimuli known to cause their endocytosis include receptor activation,drugs,and low extracellular [k+],following which the potassium channels undergo either clathrin-mediated or caveolin-mediated endocytosis. receptor-mediated endocytic regulation has been demonstrated for kv1.2,kv1.5,kcnq1 (kv7.1),and kv4.3,while drug-induced endocytosis has been demonstrated for kv1.5 and herg. low [k+]o-induced endocytosis might be unique for herg channels,whose electrophysiological characteristics are known to be under strong influence of [k+]o. although the precise mechanisms have not been elucidated,it is obvious that major cardiac voltage-dependent potassium channels are modulated by endocytosis,which leads to changes in cardiac excitability. © the japanese pharmacological society.