Referenced in: none

Automatically associated channels: Kv7.1 , Slo1

Title: Differential expression of KvLQT1 isoforms across the human ventricular wall.

Authors: Y Péréon, S Demolombe, I Baró, E Drouin, F Charpentier, D Escande

Journal, date & volume: Am. J. Physiol. Heart Circ. Physiol., 2000 Jun , 278, H1908-15

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/10843888

Abstract
Long Q-T mutant (KvLQT1) K(+) channels associate with their regulatory subunit IsK to produce the slow component of the delayed rectifier potassium (I(Ks)) cardiac current. The amplitude of KvLQT1 current depends on the expression of a KvLQT1 splice variant (isoform 2) that exerts strong dominant negative effects on the full-length KvLQT1 protein (isoform 1). We used RNase protection assays to determine the relative expression of KvLQT1 isoforms 1 and 2 and IsK mRNAs in human ventricular layers. Overall expression of KvLQT1 and IsK genes was similar in the three layers. However, there was a significant difference in the ratio between KvLQT1 isoforms 1 and 2. Isoform 2 represented 25.2 +/- 2.3%, 31.7 +/- 1.2%, and 24.9 +/- 1.7% of total KvLQT1 expression in left ventricular endocardial, midmyocardial, and epicardial tissues, respectively. Similar data were obtained from right ventricular samples. COS-7 cells were intranuclearly injected with KvLQT1 isoforms 1 or 2 plus IsK cDNAs, using two different isoform 2-to-isoform 1 ratios. Cells injected with an isoform 2-to-isoform 1 ratio mimicking that in the midmyocardium showed a K(+) current with approximately 75% reduced amplitude compared with those injected with a ratio mimicking that in the epicardium. Our results suggest that differential expression of KvLQT1 isoform 2 in endocardial, midmyocardial, and epicardial tissues is responsible for differential I(Ks) amplitude and contributes to the regional action potential heterogeneity observed across the ventricular wall.