The off rate of Ca2+ from troponin C is regulated by force-generating cross bridges in skeletal muscle

The effects of dissociation of force-generating cross bridges on intracellular Ca2+, pCa-force, and pCa-ATPase relationships were investigated in mouse skeletal muscle. Mechanical length perturbations were used to dissociate force-generating cross bridges in either intact or skinned fibers. In intact muscle, an impulse stretch or release, a continuous length vibration, a nonoverlap stretch, or an unloaded shortening during a twitch caused a transient increase in intracellular Ca2+ compared with that in isometric controls and resulted in deactivation of the muscle. In skinned fibers, sinusoidal length vibrations shifted pCa-force and pCa-actomyosin ATPase rate relationships to higher Ca2+ concentrations and caused actomyosin ATPase rate to decrease at submaximal Ca2+ and increase at maximal Ca2+ activation. These results suggest that dissociation of force-generating cross bridges during a twitch causes the off rate of Ca2+ from troponin C to increase (a decrease in the Ca2+ affinity of troponin C), thus decreasing the Ca2+ sensitivity and resulting in the deactivation of the muscle. The results also suggest that the Fenn effect only exists at maximal but not submaximal force-activating Ca2+ concentrations.

Variable series elasticity accounts for Fenn effects of skeletal and cardiac muscles

The Fenn effect differs between skeletal and cardiac muscles in the magnitude of energy consumption of shortening contraction relative to isometric contraction at the same preload. The former is typically greater than the latter in the skeletal muscle, whereas the former is smaller than the latter in the cardiac muscle. The present theoretical study examined whether the different Fenn effects could be accounted for by different compliances of the series elasticity (SE) in different muscles. A two-element model consisting of an idealized contractile element (CE) and an SE was used. The compliance of the SE was assumed to be variable. Results show that the skeletal Fenn effect can be simulated when SE is stiff and the cardiac Fenn effect can be simulated when SE is compliant. Moreover, when SE is compliant the total work of CE approximates for force-length area, which has been proposed as a measure of the total mechanical energy and shown to correlate linearly with myocardial oxygen consumption.