Slowed Dynamics of Thin Filament Regulatory Units Reduces Ca-Sensitivity of Cardiac Biomechanical Function.

Actomyosin kinetics in both skinned skeletal muscle fibers at maximum Ca-activation and unregulated motility assays are modulated by solvent microviscosity in a manner consistent with a diffusion limited process. Viscosity might also influence cardiac thin filament Ca-regulatory protein dynamics. motility assays were conducted using thin filaments reconstituted with recombinant human cardiac troponin and tropomyosin; solvent microviscosity was varied by addition of sucrose or glucose. At saturating Ca, filament sliding speed () was inversely proportional to viscosity. Ca-sensitivity ( ) of decreased markedly with elevated viscosity ( ≥ ~1.3). For comparison with unloaded motility assays, steady-state isometric force () and kinetics of isometric tension redevelopment ( ) were measured in single, permeabilized porcine cardiomyocytes when viscosity surrounding the myofilaments was altered. Maximum Ca-activated changed little for sucrose ≤ 0.3 M ( ~1.4) or glucose ≤ 0.875 M ( ~1.66), but decreased at higher concentrations. Sucrose (0.3 M) or glucose (0.875 M) decreased for . at saturating Ca decreased steeply and monotonically with increased viscosity but there was little effect on at sub-maximum Ca. Modeling indicates that increased solutes affect dynamics of cardiac muscle Ca-regulatory proteins to a much greater extent than actomyosin cross-bridge cycling.