Referenced in: none

Automatically associated channels: Kv7.1 , Nav1.5

Title: Trafficking and functional expression of cardiac Na+ channels.

Authors: Lucas J Herfst, Martin B Rook, Habo J Jongsma

Journal, date & volume: J. Mol. Cell. Cardiol., 2004 Feb , 36, 185-93

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14871545

Abstract
Voltage-gated Na(+)channels are essential for the amplitude and upstroke velocity of the cardiac action potential, which are important determinants for impulse propagation and impulse conduction velocity of throughout the working myocardium. Mutations in the major cardiac Na(+)channel gene SCN5A have been implicated in rare, familial forms of cardiac arrhythmias, namely LQT3, Brugada syndrome, progressive cardiac conduction disorder and sudden infant death syndrome. It is increasingly recognized that such mutations--apart from changing channel gating characteristics--may also be related to changes in channel protein trafficking and expression. Regulation of ion channel protein expression depends on a fine-tuned balance among various processes, such as gene transcription, RNA processing, protein synthesis, assembly and post-translational modification, the transport to the cell surface, the anchoring to the cytoskeleton, and regulation of endocytosis and controlled degradation of the protein. During the last decade, interest in factors that control the expression level of ion channels and mechanisms that are involved in targeting of channel proteins to specific sub-cellular and membrane domains is increasing. This review focuses on the current knowledge of mechanisms of cardiac Na(+) channel protein trafficking and expression in cardiomyocytes and its relation to Na(+)-channelopathies.