Skeletal muscle ion and volume regulation at rest, during contraction and recovery

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My research continues to examine mechanisms of regulating ion and fluid balance in skeletal muscle and in intact mammals. The long-term objectives are to increase the basic knowledge and understanding of the processes affecting skeletal muscle function and whole body performance during activity and recovery from activity. The short-term objectives are to: 1) continue to study the function and regulation of the skeletal muscle sodium-potassium-chloride cotransporter (NKCC); 2) to begin to study mechanisms of regulating Na,K pump activity in skeletal muscle cells recovering from contractile activity; and 3) examine the influence of high intensity exercise on muscle potassium transport pathways during both the contractile period and during recovery. We use two main experimental approaches in an integrated manner that spans from molecular to the tissue level. The first approach uses an intact isolated rat hindlimb preparation that is perfused with an artificial blood of known and constant composition. The strength of this approach is that it permits the determination of net and unidirectional ion, metabolite and fluid fluxes between vascular and muscle compartments, together with measurements of ion and metabolite changes within the stratified fiber type population of the lower rat hindlimb. The conditions closely approximate those found in vivo, yet confer the benefits of increased control of perfusate composition and the experimental paradigm. The second approach uses mouse skeletal muscle bundles or single fibres studied in vitro to determine the time course of change in intracellular ion status, membrane potential and cell volume in response hypertonic stress, ion transport activators and ion transport inhibitors. This work is expected to improve our understanding of skeletal muscle and whole animal ion and fluid regulation during rest, exercise, fatigue and recovery. It is further expected that the results will transfer to the study of muscle pathologies involving electrolyte, contractile and metabolic imbalances such as muscular dystrophy and type II diabetes.