INDUCED ADAPTATIONS IN MYOSIN PHENOTYPE AND MUSCLE MASS

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The primary hypothesis of this proposal is that changes in muscle myosin heavy chain (MHC) phenotype are mediated by processes distinct from those leading to muscle hypertrophy. A sequence of experiments will examine the role of different types of heavy resistance training paradigms in the regulation of MHC phenotype plasticity and the compensatory growth (hypertrophy) of skeletal muscle fibers. These paradigms will consist of isometric, eccentric, and concentric types of contraction, which will be applied with varying intensity and duration. We will test the hypothesis that contraction paradigms requiring slow cross bridge cycling kinetics induce up regulation of slower MHCs (chiefly type I and type IIa); whereas, contraction paradigms requiring either near maximal shortening velocities or power output induce down regulation of these same MHCs. We postulate that these transformations are mediated via altered expression of factors (receptors and auxiliary proteins) associated with thyroid hormone action. In contrast, we propose that alterations in muscle mass (myofiber cross sectional area) result from the magnitude and accumulated amount of force imposed on the muscle independent of cross bridge cycling kinetics. We propose that hypertrophic changes are mediated, in part, by an autocrine/paracrine effect of insulin-like growth factor (IGF-1) involving increased IGF-1 expression by trained muscles, thereby initiating a cascade of events leading to protein accumulation. The proposed experiments will be broken down into two phases each with multiple stages. In Phase I the first stage will examine the role of varying the tension-time integral during both isometric and eccentric contractions in mediating up regulation of type I MHC expression in fast- twitch muscle. Stage II of this phase will determine if concentric contractions maximizing the shortening velocity of the muscle down regulate type I MHC expression in antigravity muscle. Phase II will ascertain how paradigms varying force production alter muscle mass in conjunction with IGF-1 expression. Collectively, these experiments will more clearly define the role of specific mechanical factors and the corresponding subcellular factors in the regulation of MHC phenotype and muscle mass.