SCN5A channelopathies--an update on mutations and mechanisms

Prog Biophys Mol Biol. Oct-Nov 2008;98(2-3):120-36. doi: 10.1016/j.pbiomolbio.2008.10.005. Epub 2008 Nov 5.

Abstract

Voltage-gated Na+ channels mediate the rapid upstroke of the action potential in excitable tissues. Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart. Mutations in SCN5A are associated with distinct cardiac excitation disorders often resulting in life-threatening arrhythmias. This review outlines the currently known SCN5A mutations linked to three distinct cardiac rhythm disorders: long QT syndrome subtype 3 (LQT3), Brugada syndrome (BS), and cardiac conduction disease (CCD). Electrophysiological properties of the mutant channels are summarized and discussed in terms of Na+ channel structure-function relationships and regarding molecular mechanisms underlying the respective cardiac dysfunction. Possible reasons for less convincing genotype-phenotype correlations are suggested.

Publication types

  • Review

MeSH terms

  • Arrhythmias, Cardiac / etiology
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / physiopathology
  • Brugada Syndrome / genetics
  • Electrophysiological Phenomena
  • Genotype
  • Humans
  • Long QT Syndrome / classification
  • Long QT Syndrome / genetics
  • Models, Molecular
  • Muscle Proteins / chemistry
  • Muscle Proteins / genetics*
  • Muscle Proteins / physiology
  • Mutation*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Phenotype
  • Sodium Channels / chemistry
  • Sodium Channels / genetics*
  • Sodium Channels / physiology

Substances

  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels