INDUCED ADAPTATIONS IN MYOSIN PHENOTYPE AND MUSCLE MASS

这项建议的主要假设是，肌肉肌球蛋白的变化 重链（MHC）表型是由不同于那些 导致肌肉肥大一系列实验将检验 不同类型的重阻力训练模式在 MHC表型可塑性的调节和补偿性生长 骨骼肌纤维肥大。这些范例将包括 等长、偏心和同心收缩类型， 以不同的强度和持续时间施加。我们将检验这个假设 需要缓慢的跨桥循环动力学的收缩范例 诱导较慢MHC（主要是I型和IIa型）上调; 然而，收缩模式需要接近最大缩短， 速度或功率输出引起这些相同MHC的下调。我们 假设这些转化是通过改变表达介导的 与甲状腺相关的因子（受体和辅助蛋白） 激素作用。相反，我们认为肌肉质量的改变 （肌纤维横截面积）的大小和积累的结果 施加在肌肉上的力的大小与跨桥自行车运动无关 动力学我们认为，肥大性改变部分是由 胰岛素样生长因子（IGF-1）的自分泌/旁分泌作用 包括通过训练肌肉增加IGF-1表达， 引发导致蛋白质积累的级联事件。的 拟议的实验将分为两个阶段， 多个阶段在第一阶段，第一阶段将审查 在等长和偏心过程中改变张力-时间积分 收缩介导的上调I型MHC表达的快速- 抽搐肌肉。该阶段的第二阶段将确定是否同心 收缩使肌肉向下的缩短速度最大化 调节抗重力肌I型MHC表达。二期将 确定如何范式不同的力量生产改变肌肉质量， IGF-1的表达。总的来说，这些实验 更清楚地定义特定机械因素的作用以及 相应的亚细胞因子调节MHC表型， 肌肉质量.

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.