1. The effects of reduced Na+/K+ gradients and Na+-K+ pump stimulation on compound action potentials (M waves) and contractile force were examined in isolated rat soleus muscles stimulated through the nerve. 2. Exposure of muscles to buffer containing 85 mM Na+ and 9 mM K+ (85 Na+/9 K+ buffer) produced a 54% decrease in M wave area and a 50 % decrease in tetanic force compared with control levels in standard buffer containing 147 mM Na+ and 4 mM K+. Subsequent stimulation of active Na+-K+ transport, using the beta2-adrenoceptor agonist salbutamol, induced a marked recovery of M wave area and tetanic force (to 98 and 87% of the control level, respectively). Similarly, stimulation of active Na+-K+ transport with insulin induced a significant recovery of M wave area and tetanic force. 3. During equilibration with 85 Na+/9 K+ buffer and after addition of salbutamol there was a close linear correlation between M wave area and tetanic force (r = 0.92, P < 0.001). Similar correlations were found in muscles where tetrodotoxin was used to reduce excitability and in muscles fatigued by 120 s of continuous stimulation at a frequency of 30 Hz. 4. These results show a close correlation between excitability and tetanic force. Furthermore, in muscles depressed by a reduction in the Na+/K+ gradients, beta-adrenergic stimulation of the Na+-K+ pump induces a recovery of excitability which can fully explain the previously demonstrated recovery of tetanic force following Na+-K+ pump stimulation. Moreover, the data indicate that loss of excitability is an important factor in fatigue induced by high-frequency (30 Hz) stimulation.
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