Excitation-induced activation of the Na(+)-K+ pump in rat skeletal muscle

The stimulating effect of excitation on the Na(+)-K+ pump was characterized in measurements of 22Na efflux, intracellular Na+ content, 86Rb influx, and [3H]ouabain binding in isolated rat soleus muscle. Direct stimulation (10 V, 1 ms, 2 Hz) rapidly increased 22Na efflux and 86Rb influx about twofold. These effects were blocked by tetracaine and ouabain, were not associated with any significant increase in intracellular Na+, and could not be attributed to a rise in extracellular K+. The stimulation of 22Na efflux was unaffected by tubocurarine, dantrolene, trifluoperazine, or bumetanide. Stimulation at 2 Hz increased the rate of [3H]ouabain binding by approximately 120% within 1 min, indicating an early specific activation of the Na(+)-K+ pump. Stimulation at 60 Hz for 10 s increased intracellular Na+ content by 58%. Reextrusion of Na+ was complete in 2 min and could be prevented by ouabain (10(-4) M) or by cooling to 0 degrees C. It is concluded that, in rat soleus muscle, excitation leads to a rapid and pronounced (up to 15-fold) stimulation of the Na(+)-K+ pump, even at modest increases in intracellular Na+. This activation mechanism may be essential for the maintenance of transmembrane Na(+)-K+ gradients and prompt recovery of excitability during contractile activity.