Referenced in: none

Automatically associated channels: Kv7.1 , Slo1

Title: Involvement of IsK-associated K+ channel in heart rate control of repolarization in a murine engineered model of Jervell and Lange-Nielsen syndrome.

Authors: M D Drici, I Arrighi, C Chouabe, J R Mann, M Lazdunski, G Romey, J Barhanin

Journal, date & volume: Circ. Res., 1998 Jul 13 , 83, 95-102

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9670922

Abstract
The Jervell and Lange-Nielsen (JLN) syndrome affects the human cardioauditory system, associating a profound bilateral deafness with an abnormally long QT interval on the ECG. It results from mutations in KVLQT1 and ISK genes that encode the 2 subunits forming the K+ channel responsible for the cardiac and inner ear slowly activating component of the delayed rectifier K+ current (IKs). A JLN mouse model that presents typical inner ear defects has been created by knocking out the isk gene (isk-/-). This study specifically reports on the cardiac phenotype counterpart, determined in the whole animal and at mRNAs and cellular levels. Surface ECG recordings of isk-/- mice showed a longer QT interval at slow heart rates, a paradoxical shorter QT interval at fast heart rates, and an overall exacerbated QT-heart rate adaptation compared with wild-type (WT) mice. A 300-ms increase in the heart rate cycle length induces a 309+/-21% increase in the QT duration of the WT mice versus a 500+/-50% in isk-/- mice (P<0.001). It is concluded that the isk gene product and/or IKs, when present, blunts the QT adaptation to heart rate variations and that steeper QT-RR relationships reflect a greater susceptibility to arrhythmias in patients lacking IKs.