Endocytic regulation of voltage-dependent potassium channels in the heart

J Pharmacol Sci. 2012;120(4):264-9. doi: 10.1254/jphs.12r12cp. Epub 2012 Nov 20.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Arrhythmias, Cardiac / etiology
  • Caveolins / physiology
  • Clathrin / physiology
  • Dogs
  • Endocytosis / drug effects
  • Endocytosis / physiology*
  • Humans
  • Myocardium / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels, Voltage-Gated / metabolism*
  • Potassium Channels, Voltage-Gated / physiology*
  • Quinidine / pharmacology
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Anti-Arrhythmia Agents
  • Caveolins
  • Clathrin
  • Potassium Channel Blockers
  • Potassium Channels, Voltage-Gated
  • Receptors, G-Protein-Coupled
  • Quinidine