Does mavacamten reduce isometric tension and Ca2+ sensitivity in a mouse model of hypertrophic cardiomyopathy?
Mavacamten reduces contractility and Ca2+ sensitivity in a mouse model of HCM with the N47K mutation by altering cross-bridge dynamics.
Mavacamten is a pharmaceutical that binds to myosin, and it is under investigation as a therapy for some forms of heart disease. We show that mavacamten reduces isometric tension and Ca 2+ sensitivity of contraction in skinned myocardial strips from a mouse model of hypertrophic cardiomyopathy that expresses the N47K mutation in cardiac myosin regulatory light chain. Mavacamten reduces contractility by decreasing strong cross-bridge binding, partially due to faster cross-bridge nucleotide handling rates that speed up myosin detachment.
Awinda et al. (Fri,) studied this question.