Denervated frog muscle shows altered kinetics of potassium contractures as the earliest functional consequence of loss of nervous influences. We have demonstrated in single fibers that changes in temporal characteristics are responsible for weakness and calcium sensitivity of whole muscle during the earliest post-denervation stage. Our hypothesis is that several types of changes are linked through the calcium regulatory mechanisms of the muscles. We propose to explore this change and to relate it to the larger pattern of denervation sequelae by means of 1) further studies of single fiber contractures; 2) electrophysiological investigation of membrane properties, including voltage clamp; 3) tracer studies of calcium fluxes; and 4) analysis of mechanical changes during physiological activation of the muscle (twitches and tetani). Our focus will be determination of the mechanisms behind the alterations as they appear sequentially after denervation. We will employ not only frog muscle but also major types of mammalian muscle. Our study will 1) extend knowledge of excitation-contraction coupling in muscle; 2) contribute directly to understanding of changes in traumatically denervated muscle; and 3) develop a framework for studying groups of functional alterations which can be applied to other disease states of muscle, particularly those involving sarcotubular changes. BIBLIOGRAPHIC REFERENCES: Calcium Content and exchange in frog skeletal muscle. A. C. Kirby, B.D. Lindley, and J.R. Picken. J. Physiol. 253-37-52, l975. Contractile inactivation in frog single denervated muscle fibers. S. C. Stuesse and B. D. Lindley. Am. J. Physiol. 229:1492-1497, l975.