hERG K(+) Channels: Structure, Function, and Clinical Significance

Physiol Rev. 2012 Jul;92(3):1393-478. doi: 10.1152/physrev.00036.2011.

Abstract

The human ether-a-go-go related gene (hERG) encodes the pore-forming subunit of the rapid component of the delayed rectifier K(+) channel, Kv11.1, which are expressed in the heart, various brain regions, smooth muscle cells, endocrine cells, and a wide range of tumor cell lines. However, it is the role that Kv11.1 channels play in the heart that has been best characterized, for two main reasons. First, it is the gene product involved in chromosome 7-associated long QT syndrome (LQTS), an inherited disorder associated with a markedly increased risk of ventricular arrhythmias and sudden cardiac death. Second, blockade of Kv11.1, by a wide range of prescription medications, causes drug-induced QT prolongation with an increase in risk of sudden cardiac arrest. In the first part of this review, the properties of Kv11.1 channels, including biogenesis, trafficking, gating, and pharmacology are discussed, while the second part focuses on the pathophysiology of Kv11.1 channels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / chemistry
  • Ether-A-Go-Go Potassium Channels / drug effects
  • Ether-A-Go-Go Potassium Channels / genetics
  • Ether-A-Go-Go Potassium Channels / metabolism*
  • Genetic Predisposition to Disease
  • Heart Conduction System / drug effects
  • Heart Conduction System / metabolism*
  • Heart Conduction System / physiopathology
  • Humans
  • Ion Channel Gating
  • Long QT Syndrome / etiology
  • Long QT Syndrome / metabolism
  • Long QT Syndrome / physiopathology
  • Phenotype
  • Potassium / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Protein Conformation
  • Protein Transport
  • Structure-Activity Relationship

Substances

  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • Potassium Channel Blockers
  • Potassium