Distinct electrophysiological and mechanical beating phenotypes of long QT syndrome type 1-specific cardiomyocytes carrying different mutations

Publication date: 1 September 2015 Source:IJC Heart & Vasculature, Volume 8 Author(s): Anna L. Kiviaho , Antti Ahola , Kim Larsson , Kirsi Penttinen , Heikki Swan , Mari Pekkanen-Mattila , Henna Venäläinen , Kiti Paavola , Jari Hyttinen , Katriina Aalto-Setälä Background Long QT syndrome (LQTS) is associated with increased risk of ventricular arrhythmias and cardiac arrest. LQTS type 1 (LQT1), the most prevalent subtype of LQTS, is caused by defects of slow delayed rectifier potassium current (IKs) that lead to abnormal cardiac repolarization. Here we used pluripotent stem cell (iPSC)-technology to investigate both the electrophysiological and also for the first time the mechanical beating behavior of genetically defined, LQT1 specific cardiomyocytes (CMs) carrying different mutations. Methods We established in vitro models for LQT1 caused by two mutations (G589D or ivs7-2A>G). LQT1 specific CMs were derived from patient specific iPSCs and characterized for their electrophysiology using a current clamp and Ca2+-imaging. Their mechanical beating characteristics were analyzed with video-image analysis method. Results and conclusions Both LQT1-CM-types showed prolonged repolarization, but only those with G589D presented early after-depolarizations at baseline. Increased amounts of abnormal Ca2+ transients were detected in both types of LQT1-CMs. Surprisingly, also the mechanical beating behavior demonstrated clear abnormalities and additional...
Source: IJC Heart and Vasculature - Category: Cardiology Source Type: research