Ca²⁺ and segment length dependence of isometric force kinetics in intact ferret cardiac muscle

The influence of Ca²⁺ and sarcomere length on myocardial crossbridge kinetics was studied in ferret papillary muscle by measuring the rate of force redevelopment following a rapid length step that dropped the force to zero. Tetanic stimulation with 5 μmol/L ryanodine was used to obtain a steady-state contraction, and segment length was measured and controlled using a sense-coil technique that measures changes in the cross-sectional area of the central region of the muscle. The rate constant for the recovery of force (k_tr) following a rapid length release was obtained by fitting the data with a single exponential function. Contrary to results from skinned skeletal fibers in which k_tr increases almost 10-fold from low to maximal activation levels, k_tr was found not to increase at higher activation levels in this study. Similarly, although force increased with segment length under all conditions, k_tr never increased with length. Data presented here are consistent with a model of myocardial Ca²⁺ activation in which Ca²⁺ modulates the number of crossbridges interacting with the thin filament and are inconsistent with a model in which Ca²⁺ modulates the kinetics of transitions to force producing states within the actomyosin cycle. Differences in the activation dependence of the force redevelopment rate between cardiac and skeletal muscle suggest that there are fundamental differences in the mechanism of Ca²⁺ activation between these two muscle types.