The sodium pump keeps us going.
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.
Clausen
Torben
T
Department of Physiology, University of Aarhus, Denmark. tc@fi.au.dk
D000818:Animals; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium