The Na+, K+ pump in skeletal muscle: Quantification, regulation and functional significance

In skeletal muscle. the Na+, K+ pump is predominantly situated in the sarcolemma (1000-3500 pumps per mu m(2)). The total concentration can be determined in fresh or frozen biopsies (1-5 mg) using a H-3-ouabain binding assay. The values obtained have been confirmed by measurements of maximum ouabain suppressible Na+, K+-transport capacity in intact muscles as well as Na+, K+-ATPase-related enzyme activity in muscle homogenates. In the mature organism, the concentration of Na+, K+ pumps varies with muscle type and species in the range 150-600 pmol (g wet wt)(-1). In rat and human muscle. the concentration increases markedly with thyroid status. Semi-starvation and untreated diabetes reduce the concentration by 20-48%. K+ deficiency leads to a downregulation of up to 75%. Both in animals and in humans, training increases the concentration of Na+, K+ pumps in muscle. and inactivity leads to a downregulation. High-frequency stimulation elicits up to a 20-fold increase in the net efflux of Na+ within 10 s This is the major activation mechanism for the Na+, K+ pump. utilizing its entire capacity and possibly represents a drive on de novo synthesis of Na+, K+ pumps. A variety of hormones (insulin, insulin-like growth factor I, adrenaline. noradrenaline. calcitonin gene-related peptide. calcitonin. amylin) increase the rate of active Na+, K+ transport by 60-120% within a few minutes. This leads to a decrease in intracellular Na+ and hyperpolarization. In isolated muscles. where contractility is inhibited by high extracellular K+. such agents produce rapid force recovery. which is entirely suppressed by ouabain and closely correlated to the stimulation of K+ uptake and the decline in intracellular Na+. The observations support the conclusion that the Na+, K+ pump plays a central role in the acute recovery and maintenance of excitability during contractile activity.