SCN5A channelopathies--an update on mutations and mechanisms.
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.
Zimmer
Thomas
T
Institute of Physiology II, Friedrich Schiller University Jena, Kollegiengasse 9, 07743 Jena, Germany. thomas.zimmer@mti.uni-jena.de <thomas.zimmer@mti.uni-jena.de>
Surber
Ralf
R
D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D053840:Brugada Syndrome / Q000235:genetics; D055724:Electrophysiological Phenomena; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000145:classification / Q000235:genetics; D008958:Models, Molecular; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010641:Phenotype; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels