title: Endocytic regulation of voltage-dependent potassium channels in the heart.
abstract: 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.
authors.affiliation: Department of Pharmacology, Yamagata University School of Medicine, Yamagata, Japan. kuishii@med.id.yamagata-u.ac.jp
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Ishii
authors.forename: Ikuo
authors.initials: I
authors.lastname: Norota
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Obara
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000209:etiology; D022461:Caveolins / Q000502:physiology; D002966:Clathrin / Q000502:physiology; D004285:Dogs; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism* / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000889:Anti-Arrhythmia Agents; D022461:Caveolins; D002966:Clathrin; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D043562:Receptors, G-Protein-Coupled; D011802:Quinidine