RELATION BETWEEN EXTRACELLULAR [K+], MEMBRANE-POTENTIAL AND CONTRACTION IN RAT SOLEUS MUSCLE - MODULATION BY THE NA+-K+ PUMP

An increased extracellular K+ concentration ([K+](o)) is thought to cause muscle fatigue. We studied the effects of increasing [K+](o) from 4 mM to 8-14 mM on tetanic contractions in isolated bundles of fibres and whole soleus muscles from the rat. Whereas there was little depression of force at a [K+](o) of 8-9 mM, a further small increase in [K+](o) to 11-14 mM resulted in a large reduction of force. Tetanus depression at 11 mM [K+](o) was increased when using weaker stimulation pulses and decreased with stronger pulses. Whereas the tetanic force/resting membrane potential (E(M)) relation showed only moderate force depression with depolarization from -74 to -62 mV, a large reduction of force occurred when E(M) fell to -53 mV. The implications of these relations to fatigue are discussed. Partial inhibition of the Na+-K+ pump with ouabain (10(-6) M) caused additional force loss at 11 mM [K+](o) Salbutamol, insulin, or calcitonin gene-related peptide all stimulated the Na+-K+ pump in muscles exposed to 11 mM [K+](o) and induced an average 26-33% recovery of tetanic force. When using stimulation pulses of 0.1 ms, instead of the standard 1.0-ms pulses, force recovery with these agents was 41-44% which was significantly greater (P<0.025). Only salbutamol caused any recovery of E(M) (1.3 mV). The observations suggest that the increased Na+ concentration difference across the sarcolemma, following Na+-K+ pump stimulation, has an important role in restoring excitability and force.