K(+)-induced inhibition of contractile force in rat skeletal muscle: role of active Na(+)-K+ transport.

During excitation, K+ is lost from the working muscle fibers, and interfiber K+ may reach 10-15 mM. This, in turn, may lead to depolarization and impairment of contractile performance. The significance of elevated interfiber K+ was assessed by exposing rat muscles of uniform size (25 mg) to buffer containing 12.5-15 mM K+ and studying the decline in contractile performance and its recovery following restoration of the K+ concentration of the standard buffer (5.9 mM). When active Na(+)-K+ transport was partially inhibited by ouabain (10(-6)-10(-5) M leading to relative occupancies of 28 and 84%, respectively), the decrease in force development induced by high K+ in soleus was considerably accelerated and recovery was delayed. Conversely, when active Na(+)-K+ transport was stimulated by epinephrine, the beta 2-agonist salbutamol, or insulin, the exposure to high K+ gave a much slower decline in force. The time until full inhibition was closely correlated to the rate of Na(+)-K+ pump-mediated 86Rb uptake (r = 0.98; P less than 0.005). Significant retardation of K(+)-induced force decline could be detected down to 10(-8) M epinephrine or salbutamol. After restoration of 5.9 mM K+, recovery was promoted by epinephrine and salbutamol but not by insulin. In extensor digitorum longus muscle, insulin reduced the rate of force decline induced by exposure to 15 mM K+. The results indicate that the Na(+)-K+ pump plays a major role in the maintenance of contractility during the physiological acute exposure to high extracellular K+ associated with muscle work.