Diffraction patterns were obtained from the trabeculae of the rat under relaxed and activated conditions. Changes in filament separation, the fraction of myosin bound to actin and chord stiffness K by osmotic compression with Dextran T500 were determined at several sarcomere lengths. Dextran caused the separation to decrease and the fraction of myosin bound to increase, indicating increased weak crossbridge binding. This effect of increasing crossbridge binding as a function of decreasing filament separation is more prominent in cardiac muscle than in skeletal muscle. The results suggest that in intact cardiac muscle increasing sarcomere length and decreasing lattice separation could increase the probability of weak crossbridge binding and may eventually provide an explanation for the Frank-Starling Law. ? The mechanism of allosteric activators of cardiac thin filaments was also investigated. This particular study characterized the mechanical state of cross-bridges with bound sodium vanadate (Vi) as a tool to examine the contribution of cross-bridges to cardiac muscle activation. With sodium vanadate, there was a shift in cross-bridge population toward low force states with very slow attachment/detachment kinetics. Low angle x-ray diffraction measurements indicate that with Vi cross-bridge mass shifted away from thin filaments, implying decreased cross-bridge/thin filament interaction. The combined x-ray and mechanical data suggest at least two cross-bridge populations with Vi; one characteristic of normal cycling cross-bridges, and a population of weak-binding cross-bridges with bound Vi and slow attachment/detachment kinetics. The effects of Vi on force redevelopment kinetics k(TR) imply that contraction kinetics are affected not only by the intrinsic properties of the cross-bridge cycle, but also by thin filament activation.

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National Institute of Arthritis and Musculoskeletal and Skin Diseases
United States
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