Comparison of cross-bridge cycling kinetics in neonatal vs. adult rat ventricular muscle

The developmental shift in contractile protein isoform expression in the rodent heart likely affects actin-myosin cross-bridge interactions. We compared the Ca²⁺ sensitivity for force generation and cross-bridge cycling kinetics in neonatal (postnatal days 0-3) and adult (day 84) rats. The force-pCa relationship was determined in Triton-X skinned muscle bundles activated at pCa 9.0 to 4.0. In strips maximally activated at pCa 4.0, the following parameters of cross-bridge cycling were measured: (1) rate of force redevelopment following rapid shortening and restretching (k(tr)); and (2) isometric stiffness at maximal activation and in rigor. The fraction of attached cross-bridges (α(fs)) and apparent rate constants for cross-bridge attachment (f(app)) and detachment (g(app)) were derived assuming a two-state model for cross-bridge cycling. Compared to the adult, the force-pCa curve for neonatal cardiac muscle was significantly shifted to the left. Neonatal cardiac muscle also displayed significantly smaller α(fs), slower k(tr) and f(app); however, g(app) was not significantly different between age groups. These data indicate that weaker force production in neonatal cardiac muscle involves, at least in part, less efficient cross-bridge cycling kinetics.