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.
Clausen
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Institute of Physiology, University of Aarhus, Denmark.
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005260:Female; D008297:Male; D008564:Membrane Potentials; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009132:Muscles / Q000378:metabolism / Q000502:physiology; D010042:Ouabain / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012413:Rubidium / Q000493:pharmacokinetics; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D002352:Carrier Proteins; D028021:Sodium-Potassium-Chloride Symporters; D010042:Ouabain; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium