Referenced in: none

Automatically associated channels: Kv7.1

Title: Multiple mechanisms of Na+ channel--linked long-QT syndrome.

Authors: R Dumaine, Q Wang, M T Keating, H A Hartmann, P J Schwartz, A M Brown, G E Kirsch

Journal, date & volume: Circ. Res., 1996 May , 78, 916-24

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/8620612

Abstract
Inheritable long-QT syndrome (LQTS) is a disease in which delayed ventricular repolarization leads to cardiac arrhythmias and the possibility of sudden death. In the chromosome 3-linked disease, one mutation of the cardiac Na+ channel gene results in a deletion of residues 1505 to 1507 (Delta KPQ), and two mutation result in substitutions (N1325S and R1644H). We compared all three mutant-channel phenotypes by heterologous expression in Xenopus oocytes. Each produced a late phase of inactivation-resistant, mexiletine- and tetrodotoxin-sensitive whole-cell currents, but the underlying mechanisms were different at the single-channel level. N1325S and R1644H showed dispersed reopenings after the initial transient, whereas Delta KPQ showed both dispersed reopenings and long-lasting bursts. Thus, two distinct biophysical defects underlie the in vitro phenotype of persistent current in Na+ channel-linked LQTS, and the additive effects of both are responsible for making the Delta KPQ phenotype the most severe.