Cooling intact and demembranated trabeculae from rat heart releases myosin motors from their inhibited conformation

Ovejero et al. show that cooling resting or relaxed rat heart muscle releases myosin motors from the helical folded conformation that inhibits actin interaction in physiological conditions. Myosin filament-based regulation supplements actin filament-based regulation to control the strength and speed of contraction in heart muscle. In diastole, myosin motors form a folded helical array that inhibits actin interaction; during contraction, they are released from that array. A similar structural transition has been observed in mammalian skeletal muscle, in which cooling below physiological temperature has been shown to reproduce some of the structural features of the activation of myosin filaments during active contraction. Here, we used small-angle x-ray diffraction to characterize the structural changes in the myosin filaments associated with cooling of resting and relaxed trabeculae from the right ventricle of rat hearts from 39 degrees C to 7 degrees C. In intact quiescent trabeculae, cooling disrupted the folded helical conformation of the myosin motors and induced extension of the filament backbone, as observed in the transition from diastole to peak systolic force at 27 degrees C. Demembranation of trabeculae in relaxing conditions induced expansion of the filament lattice, but the structure of the myosin filaments was mostly preserved at 39 degrees C. Cooling of relaxed demembranated trabeculae induced changes in motor conformation and filament structure similar to those observed in intact quiescent trabeculae. Osmotic compression of the filament lattice to restore its spacing to that of intact trabeculae at 39 degrees C stabilized the helical folded state against disruption by cooling. The myosin filament structure and motor conformation of intact trabeculae at 39 degrees C were largely preserved in demembranated trabeculae at 27 degrees C or above in the presence of Dextran, allowing the physiological mechanisms of myosin filament-based regulation to be studied in those conditions.

Automated summary

In this study, the researchers found that cooling the rat heart muscle can release myosin motors, which affects the strength and speed of contraction. Additionally, they observed similar structural changes in relaxed conditions when cooling was applied.