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

摘要

In rat skeletal muscle, Na⁺–K⁺ pump activity increases dramatically in response to excitation (up to 20-fold) or β2-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 30 ^oC in Krebs-Ringer bicarbonate buffer. The effects of direct electrical stimulation on ⁸⁶Rb⁺ 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 β2-agonist salbutamol and electrical stimulation produced a left shift of the curves relating ⁸⁶Rb⁺ 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 ⁸⁶Rb⁺ 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 ⁸⁶Rb⁺ uptake rate and decrease in [Na⁺]i. Na⁺ loading induced by monensin or electroporation also stimulated ⁸⁶Rb⁺ uptake rate but, contrary to excitation, increased [Na⁺]i. The increase in the rate of ⁸⁶Rb⁺ 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.