Arrhythmia phenotype in mouse models of human long QT.

Journal of Interventional Cardiac Electrophysiology : an International Journal of Arrhythmias and Pacing
Guy SalamaB London

Abstract

Enhanced dispersion of repolarization (DR) was proposed as a unifying mechanism, central to arrhythmia genesis in the long QT (LQT) syndrome. In mammalian hearts, K(+) channels are heterogeneously expressed across the ventricles resulting in 'intrinsic' DR that may worsen in long QT. DR was shown to be central to the arrhythmia phenotype of transgenic mice with LQT caused by loss of function of the dominant mouse K(+) currents. Here, we investigated the arrhythmia phenotype of mice with targeted deletions of KCNE1 and KCNH2 genes which encode for minK/IsK and Merg1 (mouse homolog of human ERG) proteins resulting in loss of function of I(Ks) and I(Kr), respectively. Both currents are important human K(+) currents associated with LQT5 and LQT2. Loss of minK, a protein subunit that interacts with KvLQT1, results in a marked reduction of I(Ks) giving rise to the Jervell and Lange-Nielsen syndrome and the reduced KCNH2 gene reduces MERG and I(Kr). Hearts were perfused, stained with di-4-ANEPPS and optically mapped to compare action potential durations (APDs) and arrhythmia phenotype in homozygous minK (minK(-/-)) and heterozygous Merg1 (Merg(+/-)) deletions and littermate control mice. MinK(-/-) mice has similar APDs and no arrhythm...Continue Reading

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Citations

Apr 7, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Eric C LinCraig T January
May 17, 2011·Cardiac Electrophysiology Clinics·Guy Salama, Fadi G Akar
Oct 20, 2012·Journal of Molecular and Cellular Cardiology·Mu QinCongxin Huang
Jan 26, 2018·Journal of Cardiovascular Development and Disease·Tanya A Baldwin, Carmen W Dessauer
Dec 16, 2016·Physiological Reviews·Christopher L-H Huang

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