P17 - Patient-specific induced pluripotent stem cell models to elucidate the role of TRP channels in the pathogenesis of CPVT1 and of PFHBI
TRPM4 channels are Ca2+ activated, non-selective cation channels that participate in a plethora of cardiac functions including the myocyte's electrical excitability. Dominantly inherited mutations in the TRPM4 gene are associated with several forms of cardiac arrhythmias and conduction diseases. We identified TRPM4’s Ca2+-dependent gating behavior as a novel contributor to the aberrant membrane current and introduced that as the causal mechanism of TRPM4 mutation dependent human arrhythmia. Taking advantage of CRISPR/Cas9-mediated TRPM4 knock-out hiPSC lines, hiPSC-derived 3D cardiac organoids and engineered heart patches , this project aims at investigating how exactly TRPM4 mutations contribute to malfunction of the heart and whether functional characteristics of TRPM4 mutants correlate with a specific clinical phenotype.
