Molecular biology of sodium channels and their role in cardiac arrhythmias.

Published

Journal Article (Review)

The sodium channel is an integral membrane protein that plays a central role in conduction of the cardiac impulse in working cardiac myocytes and cells of the His-Purkinje system. The channel has two fundamental properties, ion conduction and gating. Specific domains of the channel protein control each of these functions. Ion conduction describes the mechanisms of the selective movement of sodium ion across the pore in the cell membrane. The selectivity of the channel for sodium ions is at least 10 times greater than that for other monovalent cations; the channel does not normally conduct divalent cations. Gating describes the opening and closing of the sodium channel pore. Sodium channels open transiently during membrane depolarization and close by a process termed inactivation. The cardiac sodium channel protein is a multimeric complex consisting of an alpha and an auxiliary beta-subunit. The genes encoding the sodium channel have been cloned and sequenced. The alpha subunit gene, SCN5A is sufficient to express a functional channel. However, beta subunit co-expression increases the level of channel expression and alters the voltage dependence of inactivation. Mutations of the sodium channel may result in incomplete inactivation during maintained depolarization, a decrease in the level of channel expression or acceleration of inactivation. The resulting clinical phenotypes include long QT syndrome, type III (LQT III), Brugada syndrome, and heart block. LQT III and Brugada syndromes have a high case fatality rate and are best treated with an implantable defibrillator.

Full Text

Duke Authors

Cited Authors

  • Grant, AO

Published Date

  • March 2001

Published In

Volume / Issue

  • 110 / 4

Start / End Page

  • 296 - 305

PubMed ID

  • 11239848

Pubmed Central ID

  • 11239848

Electronic International Standard Serial Number (EISSN)

  • 1555-7162

International Standard Serial Number (ISSN)

  • 0002-9343

Digital Object Identifier (DOI)

  • 10.1016/s0002-9343(00)00714-2

Language

  • eng