Effects of exercise, renal disease, and digoxin on skeletal muscle Na+,K+-ATPase and related effects on plasma K+ and muscle performance

Abstract

In skeletal muscle, the Na+,K+-ATPase enzyme regulates trans-membrane Na+ and K+ fluxes during contractions, and therefore also affects muscle excitability and plays an important role in delaying muscle fatigue. Consequently, any modulation of Na+,K+-ATPase content or activity has the potential to affect muscle fatiguability. Thus, this thesis investigated three factors thought to impair or down-regulate the skeletal muscle Na+,K+-ATPase – acute exercise, renal disease and digoxin. The related effects on plasma [K+] during exercise and on muscle performance were also examined. This thesis firstly investigated the acute effects of brief intense exercise on muscle Na+,K+-ATPase content and maximal activity (Study 1). Study 2 investigated the effects of end-stage renal disease on plasma [K+] regulation during exercise; examined the relationship between impaired [K+] regulation and muscle performance, and investigated the effects of endurance training in these patients. Study 3 investigated the impacts of end-stage renal disease and renal transplantation on skeletal muscle Na+,K+-ATPase and its relationship with muscle performance. Finally, Study 4 investigated the effects of chronic digoxin administration on skeletal muscle Na+,K+-ATPase content and maximal activity and on muscle performance in healthy humans.