Muscle Physiology Research Laboratory

Research

Skeletal muscle is a tissue that will readily adapt to chronic changes in loading and neural activation. Increased load and activation results in muscle hypertrophy, while atrophy occurs with a reduction in load and neural activity. The most obvious phenotypical change with hypertrophy and atrophy are respective increases and decreases in muscle mass and fiber cross-sectional area. Despite the well-known outward characteristics of a hypertrophying or atrophying fiber, little is known about the basic mechanisms of muscle fiber adaptation. The overriding goal of research performed in our lab is to elucidate the cellular and molecular adaptations of skeletal muscle to changes in loading and neural activation.

We study various in vivo and in vitro models of increased loading such as muscle stretch and exercise training and models of reduced muscle activation such as denervation and spinal cord injury. One line of research has utilized an in vivo gene injection technique into rat skeletal muscle to study regulation of myosin heavy chain (MHC) gene expression under different loading conditions. Myosin is one of the major contractile proteins in skeletal muscle and provides the majority of functional diversity among muscles; thus, changes in MHC gene expression ultimately change the contractile properties of the muscle. We have characterized important elements in the slow type I MHC gene promoter that regulate this gene in response to chronic muscle inactivity with spinal cord injury or denervation. Recent work has focused on the role of small heat shock proteins (HSP) in skeletal muscle adaptation. All tissues, including muscle, have endogenous defense mechanisms to rapidly respond to various types of stressors, such as muscle overuse or disuse. A major component of this defense is the family of HPPs, which can assist in the maintenance of protein synthesis rates, refold damaged proteins, scavenge free radicals, and inhibit apoptosis. All these functions may contribute to muscle mass regulation which depends upon the relative rates of protein synthesis vs. degradation. Current studies are investigating changes in the expression of HSP25 and HSP20 in response to increased or decreased muscle loading, in vivo. These experiments have provided the physiological basis for experiments utilizing in vitro stretch (or shortening) to directly study signaling pathways involving HSP25 and HSP20 and their effects on muscle mass and function. Studies are also planned to investigate how the HSPs may protect the muscle against the damaging loss of muscle mass associated with elevated levels of the pro-inflammatory cytokines (e.g. tumor necrosis factor a) and/or cortisol, such as occurs with aging or disease. Overall, our research has implications in several areas such as the benefits of exercise and training and the effects of aging and inactivity on our muscles.