Excitation- and β2-agonist-induced activation of the Na+-K+ pump in rat soleus muscle

In rat skeletal muscle, Na+-K+ pump activity increases dramatically in response to excitation (up to 20-fold) or beta(2)-agonists (2-fold), leading to a reduction in intracellular Na+. This study examines the time course of these effects and whether they are due to an increased affinity of the Na+-K+ pump for intracellular Na+. Isolated rat soleus muscles were incubated at 30degreesC in Krebs-Ringer bicarbonate buffer. The effects of direct electrical stimulation on Rb-86(+) uptake rate and intracellular Na+ concentration ([Na+](i)) were characterized in the subsequent recovery phase. [Na+](i) was varied using monensin or buffers with low Na+. In the [Na+](i) range 21-69 mm, both the beta(2)-agonist salbutamol and electrical stimulation produced a left shift of the curves relating Rb-86(+) uptake rate to [Na+](i). In the first 10 s after 1 or 10 s pulse trains of 60 Hz, [Na+](i) showed no increase, but Rb-86(+) uptake rate increased by 22 and 86%, respectively. Muscles excited in Na+-free Li+-substituted buffer and subsequently allowed to rest in standard buffer also showed a significant increase in Rb-86(+) uptake rate and decrease in [Na+](i). Na+ loading induced by monensin or electroporation also stimulated Rb-86(+) uptake rate but, contrary to excitation, increased [Na+](i). The increase in the rate of Rb-86(+) uptake elicited by electrical stimulation was abolished by ouabain, but not by bumetanide. The results indicate that excitation (like salbutamol) induces a rapid increase in the affinity of the Na+-K+ pump, for intracellular Na+. This leads to a Na+-K+ pump activation that does not require Na+ influx, but possibly the generation of action potentials. This improves restoration of the Na+-K+ homeostasis during work and optimizes excitability and contractile performance of the working muscle.