The Na+,K+ pump and muscle excitability

In most types of mammalian skeletal muscles the total concentration of Na+,K+ pumps is 0.2-0.8 nmol g wet wt(-1). At rest, only around 5% of these Na+,K+ pumps are active, but during high-frequency stimulation, Virtually all Na+,K+ pumps may be called into action within a few seconds. Despite this large capacity for active Na+,K+ transport, excitation often induces a net loss of K+, a net gain of Na+, depolarization and ensuing loss of excitability. In muscles exposed to high [K+](o) or low [Na+](o), alone or combined, excitability is reduced. Under these conditions, hormonal or excitation-induced stimulation of the Na+,K+ pump leads to considerable force recovery. This recovery can be blocked by ouabain and seems to be the result of Na+,K+ pump induced hyperpolarization and restoration of Na+,K+ gradients. in muscles where the capacity of the Na+,K+ bump is reduced, the decline in the force developing during continuous electrical stimulation (30-90 Hz) is accelerated and the subsequent force recovery considerably delayed. The loss of endurance is significant within a few seconds after the onset of stimulation. Increased concentration of Na+ channels or open-time of Na+ channels is also associated with reduced endurance and impairment of force recovery. This indicates that during contractile activity, excitability is acutely dependent on the ratio between Na+ entry and Na+,K+ pump capacity. Contrary to previous assumptions, the Na+,K+ pump, due to rapid activation of its large transport capacity seems to play a dynamic role in the from second to second restoration and maintenance of excitability in working skeletal muscle.