This project extends its previous work on excitation-contraction coupling (ECC) and relaxation coupling (RC) in skeletal muscles of the frog and mammals so as to determine the mechanisms of these processes and their interactions that determine the flux of activator Ca2 ion which regulates the contraction-relaxation cycle of the twitch and the tetanus. The studies of ECC, which depended in previous work on general electromechanical correlations in twitch and contracture, are now sharpened by concentration on the electromechanical "transforms" which specifically distinguish between the mechanical effects of the rising and falling phases of the spike, and which will be used to determine possible mechanisms by which the mechanical threshold and the duration of the action potential modulate processes of ECC so as to cause the release of activator Ca2 ion which sets up the active state. It is planned especially to determine, the role in ECC of Ca in T tubule action and to test further whether the latency relaxation is a sign of the release of Ca2 ion by the SR. The role of the T tubules in generating the action potential, and especially their possible role in causing delayed rectification, will be investigated by studying action potentials and membrane current/voltage relations of osmotically detubulated fibers, which are tested with various agents that alter the rate of rise or fall of the spike. A new active state theory will be used for tracing the course of twitch and tetanus activity in relation to the flux of Ca2 ion as inferred from the ECC electromechanical transforms, and by possible manifestations of RC and regenerative Ca-release. The course of activity in a twitch will be traced in an activated fiber by a new quick release procedure. The above general procedures will be used to determine ECC, RC and active state course in normal and denervated, slow and fast, mammalian muscles. And certain special studies are planned to determine whether mouse muscular dystrophy has a neurogenic or myogenic etiology.