FACTORS REGULATING PROPERTIES OF SKELETAL MUSCLE

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Contractile and biochemical properties of skeletal muscles of immature and adult animals are dependent on the activity patterns of the muscles in accordance with normal functional demands. The relationships between specific protein compositions and the contractile properties of individual muscle cells are beginning to be understood. However, the physiological factors that regulate myofibrillar protein composition and, therefore, contractile properties during development and in adult muscle are less well understood. The long-term goal of this project is to determine which factors are important in the regulation of skeletal muscle activity and the effects that these factors have on the expression of contractile and biochemical characteristics of single muscle cells. The activity of skeletal muscle will be experimentally altered using functional overload, hindlimb suspension to induce hypokinesia and chronic in situ stimulation using different patterns of electrical stimulation. Contractile and biochemical measurements will be made on transformed muscles and compared to those obtained from control muscles. The contractile properties to be studied are the maximal velocity of shortening, the tension generating ability and tension/pea relationships of single, skinned muscle fibers. The protein composition will be assessed using ultrasensitive gel electrophoresis and immunoblotting techniques with monoclonal antibodies against specific myosin heavy chains. Measurements will be performed on single muscle fibers that have had their surface membranes removed using a chemical skinning procedure to allow direct control of activation with Ca2+. In those cases where the individual fibers are too small for satisfactory measurements (e.g., embryonic muscle), whole muscles will be studied. The design of the experiments will permit the determination of molecular structure-function relationships in muscle by identifying associations between specific contractile properties and protein compositions of developing, adult and transformed muscle An examination of the adaptability of skeletal muscle In response to alterations in functional demands (as during chronic exercise) should improve our understanding of the physiological regulation of skeletal muscle performance. This information should be extremely valuable for the design of neural prostheses which are used to facilitate or restore motor function in certain clinical situations.