Effects of reduced electrochemical Na+ gradient on contractility in skeletal muscle: Role of the Na+-K+ pump

Continued excitation of skeletal muscle may induce a combination of a low extracellular Na+ concentration ([Na+](o)) and a high extracellular K+ concentration ([K+](o)) in the T-tubular lumen, which may contribute to fatigue. Here, we examine the role of the Na+-K+ pump in the maintenance of contractility in isolated rat soleus muscles when the Na+, K+ gradients have been altered. When [Na+](o) is lowered to 25 mM by substituting Na+ with choline, tetanic force is decreased to 30% of the control level after 60 min. Subsequent stimulation of the Na+-K+ pump with insulin or catecholamines induces a decrease in [Na+](i) and hyperpolarization. This is associated with a force recovery to 80-90% of the control level which can be abolished by ouabain. This force recovery depends on hyperpolarization and is correlated to the decrease in [Na+](i) (r = 0.93; P<0.001). The inhibitory effect of a low [Na+](o) on force development is considerably potentiated by increasing [K+](o). Again, stimulation of the Na+-K+ pump leads to rapid force recovery. The Na+-K+ pump has a large potential for rapid compensation of the excitation-induced rundown of Na+, K+ gradients and contributes, via its electrogenic effect, to the membrane potential. We conclude that these actions of the Na+-K+ pump are essential for the maintenance of excitability and contractile force.