Structural and functional impact of troponin C-mediated Ca²⁺ sensitization on myofilament lattice spacing and cross-bridge mechanics in mouse cardiac muscle.

ABSTRACT: Acto-myosin cross-bridge kinetics are important for beat-to-beat regulation of cardiac contractility; however, physiological and pathophysiological mechanisms for regulation of contractile kinetics are incompletely understood. Here we explored whether thin filament-mediated Ca²⁺ sensitization influences cross-bridge kinetics in permeabilized, osmotically compressed cardiac muscle preparations. We used a murine model of hypertrophic cardiomyopathy (HCM) harboring a cardiac troponin C (cTnC) Ca²⁺-sensitizing mutation, Ala8Val in the regulatory N-domain. We also treated wild-type murine muscle with bepridil, a cTnC-targeting Ca²⁺ sensitizer. Our findings suggest that both methods of increasing myofilament Ca²⁺ sensitivity increase cross-bridge cycli

SUBMITTER: Gonzalez-Martinez D 

PROVIDER: S-EPMC6282743 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature