Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle

The goal of this mini-review is to summarize findings concerning the role t hat different models of muscular activity and inactivity play in altering g ene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of exam ining parallel findings concerning the role that thyroid hormone (T-3, 3,5, 3'-triiodothyronine) plays in MHC expression. Findings show that both cardi ac and skeletal muscles of experimental animals are initially undifferentia ted at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T-3/activity level-dependent fash ion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta -MHC isoform, which function s to economize circulatory function in the face of altered energy demand. I n skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidi sm or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance ex ercise. The regulation of MHC gene expression by T-3 or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-report er constructs. However, the mechanisms by which T-3 and mechanical stimuli exert their control on transcriptional processes appear to be different. Ad ditional findings show that individual skeletal muscle fibers have the gene tic machinery to express simultaneously all of the adult MHCs, e.g., slow t ype I and fast IIa, IIx, and IIb, in unique combinations under certain expe rimental conditions. This degree of heterogeneity among the individual fibe rs would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and t he underlying mechanisms governing the transcriptional/translational machin ery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.