The Sodium Pump Keeps Us Going

A bstract : This invited lecture reviews recent evidence that, in skeletal muscle, excitability and contractility depend on the transmembrane distribution of Na + and K + and the membrane potential, which in turn are determined by the operation of the Na + ‐K + pump. Action potentials are elicited by passive fluxes of Na + and K + . Because of their size and sudden onset, these transport events constitute the major challenge for the Na + ‐K + pumps. When the Na + ‐K + pumps cannot readily restore the Na + ‐K + gradients, working muscle cells often undergo net loss of K + and gain of Na + . This leads to loss of excitability and force, in particular, in muscles where excitation‐induced passive Na + ‐K + fluxes are large. Thus, excitability depends on the leak/pump ratio for Na + and K + . When this ratio is increased by inhibition or downregulation of the Na + ‐K + pumps, the force decline seen during continued stimulation is accelerated. This effect is highly significant already within the first seconds of electrical stimulation. Fortunately, electrical stimulation also increases Na + ‐K + pumping rate within seconds. Thus, maximum increase (20‐fold above the resting level) may be reached in 10 seconds, with utilization of all available Na + ‐K + pumps. In muscles, where excitability was inhibited by exposure to high [K + ] o (10‐12.5 mM), activation of the Na + ‐K + pumps by hormones or electrical stimulation restored excitability and contractile force. In working muscles, the Na + ‐K + pumps, because of rapid activation of their large transport capacity, play a dynamic regulatory role in the second‐to‐second ongoing restoration and maintenance of excitability and force. The Na + ‐K + pumps become a limiting factor for contractile endurance, in particular, if their capacity is reduced by inactivity or disease.