Calcium-activated muscle from hypertrophied rabbit hearts. Mechanical and correlated biochemical changes.

Abstract

SUMMARY A chemically skinned ventricular preparation was used to investigate the contribution of altered crossbridge kinetics to the depressed rate of shortening associated with cardiac hypertrophy. Hypertrophy was produced by sustained pulmonary constriction. Multicellular bundles from control and hypertrophied right ventricles of rabbit hearts were treated with Brij-58 (a non-ionic detergent) and directly activated with solutions containing calcium. Bundles obtained from control (C) hearts did not differ significantly from bundles taken from hypertrophied (H) hearts in stiffness or in response to Ca1+ under isometric conditions. Mean activation range was approximately 10~* to 10* M Ca 1+, with half-maximal activation at 5 x 10' M Ca1+. Isometric tension Po of H bundles (4.1 ± 1.8 g/mm1, at 104 M Ca1+, 22 ± 1°C) was not significantly different from that of C bundles. In contrast, the isotonic shortening rate (following a damped release from Po to a given load) of H bundles was significantly lower than that of C bundles. Mean unloaded velocity of shortening Vo, extrapolated from the linearized form of the Hill hyperbolic equation, was 1.87 muscle lengths/sec for C bundles and 1.24 muscle lengths/sec for H bundles, a 34% reduction. Chemical studies also were carried out in ventricles used for the mechanical experiments. The Ca1+- and actin-stimulated ATPase activities of H myosin were significantly depressed (by 39% and 33%, respectively) compared with the C values, whereas there was no observed difference in (K +)EDTA-stimulated ATPase activity. We conclude that the 34% reduction in shortening velocity of H bundles as well as the depression in Ca 1+- and actin-activated ATPase activity of myosin from these same hearts probably reflect a decrease in the rate of myosin crossbridge cycling during shortening. Circ Res 44: 279-287, 1979