Mavacamten decreases maximal force and Ca<sup>2+</sup> sensitivity in the N47K-myosin regulatory light chain mouse model of hypertrophic cardiomyopathy
Peter O. Awinda, Marissa Watanabe, Yemeserach Bishaw, Anna M. Huckabee, Keinan B. Agonias, Katarzyna Kaźmierczak, Danuta Szczesna‐Cordary, Bertrand C.W. Tanner
Abstract
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.
Topics & Concepts
Hypertrophic cardiomyopathyInternal medicineImmunoglobulin light chainMyosinCardiologyBiophysicsChemistryMedicineBiologyGeneticsAntibodyCardiomyopathy and Myosin StudiesMuscle Physiology and DisordersCardiovascular Effects of Exercise