The regulation of the Na+,K+ pump in contracting skeletal muscle.
Increased passive Na+,K+ fluxes necessitate an efficient activation of the Na+,K+ pump in working muscles to limit the rundown of the Na+,K+ chemical gradients and ensuing loss of excitability. Several studies have demonstrated an increase in Na+,K+-pump rate in working muscles, and in electrically stimulated muscles up to a 22-fold increase in active Na+,K+ transport has been observed. Excitation-induced increase in intracellular Na+ is believed to be the primary stimulus for Na+,K+ pumping in a contracting muscle. In muscles recovering from electrical stimulation, however, the activity of the pump may stay elevated even after intracellular Na+ has been reduced to below the resting level. Moreover, in rat soleus muscles 10-s stimulation at 60 Hz induced a 5-fold increase in the activity of the Na+,K+ pump although mean intracellular [Na+] was unchanged. These findings strongly suggest that a substantial part of the excitation-induced increase in Na+,K+-pump activity is caused by mechanisms other than increased intracellular [Na+]. The mechanism behind this activation is not clear, but may involve a change in the affinity of the Na+,K+ pump for intracellular Na+. In addition to intracellular [Na+], the Na+,K+ pump may be stimulated in contracting muscles by other factors such as catecholamines, calcitonin gene-related peptide (CGRP), free fatty acids and cytoskeletal links. Together, this activation may form a feed forward mechanism protecting muscles from loss of excitability during periods of contraction by increasing Na+,K+-pump activity prior to erosion of the Na+,K+ chemical gradients. During exercise of high intensity, however, intracellular [Na+] increases substantially constituting an additional stimulus for the pump.
Nielsen
O B
OB
Department of Physiology, University of Aarhus, Arhus, Denmark.
Harrison
A P
AP
D000818:Animals; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000254:Sodium-Potassium-Exchanging ATPase