Referenced in: none

Automatically associated channels: Kv7.1 , Nav1.5

Title: Molecular mechanism for an inherited cardiac arrhythmia.

Authors: P B Bennett, K Yazawa, N Makita, A L George

Journal, date & volume: Nature, 1995 Aug 24 , 376, 683-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7651517

Abstract
In the congenital long-QT syndrome, prolongation of the cardiac action potential occurs by an unknown mechanism and predisposes individuals to syncope and sudden death as a result of ventricular arrhythmias. Genetic heterogeneity has been demonstrated for autosomal dominant long-QT syndrome by the identification of multiple distinct loci, and associated mutations in two candidate genes have recently been reported. One form of hereditary long QT (LQT3) has been linked to a mutation in the gene encoding the human heart voltage-gated sodium-channel alpha-subunit (SCN5A on chromosome 3p21). Here we characterize this mutation using heterologous expression of recombinant human heart sodium channels. Mutant channels show a sustained inward current during membrane depolarization. Single-channel recordings indicate that mutant channels fluctuate between normal and non-inactivating gating modes. Persistent inward sodium current explains prolongation of cardiac action potentials, and provides a molecular mechanism for this form of congenital long-QT syndrome.