The Na+,K(+)-pump and muscle contractility.

In skeletal muscle, the excitation induced influx of Na+ and efflux of K+ may be sufficient to exceed the activity or even the capacity of the available Na+,K(+)-pumps. This leads to a rise in intracellular Na+ and extracellular K+. Both events interfere with excitability and may present important limitations for the continuation of contractile activity. Furthermore, inhibition of the Na+,K(+)-pump or reduction of the concentration of functional Na+,K(+)-pumps decrease excitability and the maintenance of force during continued stimulation. Conversely, in muscles where contractile force is inhibited by exposure to high extracellular K+, acute stimulation of the Na+,K(+)-pump with catecholamines, CGRP or insulin leads to a rapid recovery of force. The large passive fluxes of Na+ and K+ associated with excitation constitute the major drive on the activity of the Na+,K(+)-pump, giving rise to up to 20-fold stimulation of the transport rate. In keeping with this, training induces an upregulation of the total concentration of Na+,K(+)-pumps in skeletal muscle. The activity and the capacity of the Na+,K(+)-pump are important limiting factors determining the maintenance of excitability and contractile performance.