Potassium, Na+,K+-pumps and fatigue in rat muscle

During contractile activity, skeletal muscles undergo a net loss of cytoplasmic K+ to the interstitial space. During intense exercise, plasma K+ in human arterial blood may reach 8 mM, and interstitial K+ 10-12 mM. This leads to depolarization, loss of excitability and contractile force. However, little is known about the effects of these physiological increases in extracellular K+ ([K+](o)) on contractile endurance. Soleus muscles from 4-week-old rats were mounted on transducers for isometric contractions in Krebs-Ringer bicarbonate buffer containing 4-10 mM K+, and endurance assessed by recording the rate of force decline during continuous stimulation at 60 Hz. Increasing [K+](o) from 4 to 8 or 10 mM and equilibrating the muscles for 40 or 20 min augmented the rate of force decline 2.4-fold and 7.2-fold, respectively (P < 0.001). The marked loss of endurance elicited by exposure to 8 or 10 mM K+ was alleviated or significantly reduced by stimulating the Na+,K+-pumps by intracellular Na+ loading, the beta(2)-agonist salbutamol, adrenaline, calcitonin gene related peptide, insulin or repeated excitation. In conclusion, excitation-induced increase in [K+](o) is an important cause of high-frequency fatigue, and the Na+,K+-pumps are essential for the maintenance of contractile force in the physiological range of [K+](o). Recordings of contractile force during continuous stimulation at 8-10 mM K+ may be used to analyse the effects of agents or conditions influencing the excitability of working isolated muscles.