What Does Chronic Electrical Stimulation Teach Us About Muscle Plasticity?

The model of chronic low-frequency stimulation for the study of muscle plasticity was developed over 30 years ago. This protocol leads to a transformation of fast, fatigable muscles toward slower, fatigue-resistant ones. It involves qualitative and quantitative changes of all elements of the muscle fiber studied so far. The multitude of stimulation-induced changes makes it possible to establish the full adaptive potential of skeletal muscle. Both functional and structural alterations are caused by orchestrated exchanges of fast protein isoforms with their slow counterparts, as well as by altered levels of expression. This remodeling of the muscle fiber encompasses the major, myofibrillar proteins, membrane-bound and soluble proteins involved in Ca2+ dynamics, and mitochondrial and cytosolic enzymes of energy metabolism. Most transitions occur in a coordinated, time-dependent manner and result from altered gene expression, including transcriptional and posttranscriptional processes. This review summarizes the advantages of chronic low-frequency stimulation for studying activity-induced changes in phenotype, and its potential for investigating regulatory mechanisms of gene expression. The potential clinical relevance or utility of the technique is also considered.