Referenced in: none

Automatically associated channels: Kv7.1 , Slo1

Title: A dominant negative isoform of the long QT syndrome 1 gene product.

Authors: S Demolombe, I Baró, Y Péréon, J Bliek, R Mohammad-Panah, H Pollard, S Morid, M Mannens, A Wilde, J Barhanin, F Charpentier, D Escande

Journal, date & volume: J. Biol. Chem., 1998 Mar 20 , 273, 6837-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9506986

Abstract
Mutations in the KvLQT1 gene are the cause of the long QT syndrome 1. KvLQT1 gene product is associated with the regulator protein IsK to produce a component of the delayed rectifier K+ current in cardiac myocytes. We identified an N-terminal truncated isoform of the KvLQT1 gene product, referred to as isoform 2. In RNase protection assays, isoform 2 represented 28.1 +/- 0.6% of the total KvLQT1 expression in the human adult ventricle. COS-7 cells injected intranuclearly with KvLQT1 isoform 1 cDNA exhibited a fast-activating K+ current, whereas those injected with a KvLQT1 isoform 1 plus IsK cDNA showed a slow-activating K+ current. Cells injected with KvLQT1 isoform 2 plasmid showed no detectable K+ current. Those injected with a 1/1 isoform 2/isoform 1 ratio showed no detectable K+ current. Those injected with 1/5 and 2/5 ratios showed a K+ current with markedly reduced amplitude. Coexpression of the IsK regulator consistently reduced the dominant negative effects of isoform 2. Our results indicate that KvLQT1 isoform 2 exerts a pronounced negative dominance on isoform 1 channels and that the cardiac KvLQT1 K+ channel complex is composed of at least three different proteins as follows: isoform 1, isoform 2, and IsK.