Heritable arrhythmias associated with abnormal function of cardiac potassium channels

Cardiovasc Res. 2020 Jul 15;116(9):1542-1556. doi: 10.1093/cvr/cvaa068.

Abstract

Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentrations of intracellular sodium, calcium, and ATP/ADP. Here, we review the diversity and functional roles of cardiac potassium channels under normal conditions and how heritable mutations in the genes encoding these channels can lead to distinct arrhythmias. We briefly review atrial fibrillation and J-wave syndromes. For long and short QT syndromes, we describe their genetic basis, clinical manifestation, risk stratification, traditional and novel therapeutic approaches, as well as insights into disease mechanisms provided by animal and cellular models.

Keywords: Atrial fibrillation; Long QT syndrome; Potassium channels; Short QT syndrome; Sudden cardiac death.

Publication types

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

MeSH terms

  • Action Potentials
  • Animals
  • Anti-Arrhythmia Agents / therapeutic use
  • Arrhythmias, Cardiac / drug therapy
  • Arrhythmias, Cardiac / genetics
  • Arrhythmias, Cardiac / metabolism*
  • Arrhythmias, Cardiac / physiopathology
  • Atrial Fibrillation / drug therapy
  • Atrial Fibrillation / genetics
  • Atrial Fibrillation / metabolism*
  • Atrial Fibrillation / physiopathology
  • Genetic Predisposition to Disease
  • Heart Rate* / drug effects
  • Heredity
  • Humans
  • Long QT Syndrome / drug therapy
  • Long QT Syndrome / genetics
  • Long QT Syndrome / metabolism*
  • Long QT Syndrome / physiopathology
  • Mutation
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Phenotype
  • Potassium / metabolism*
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Prognosis
  • Risk Assessment
  • Risk Factors

Substances

  • Anti-Arrhythmia Agents
  • Potassium Channels
  • Potassium

Supplementary concepts

  • Short Qt Syndrome