Na(+)-K+ pump stimulation elicits recovery of contractility in K(+)-paralysed rat muscle.

1. This study explores the role of active electrogenic Na(+)-K+ transport in restoring contractility in isolated rat soleus muscles exposed to high extracellular potassium concentration ([K+]o). This was done using agents (catecholamines and insulin) known to stimulate the Na(+)-K+ pump via different mechanisms. 2. When exposed to Krebs-Ringer bicarbonate buffer containing 10 mM K+, the isometric twitch and tetanic force of intact muscles decreased by 40-69%. The major part of this decline could be prevented by the addition of salbutamol (10(-5) M). In the presence of 10 mM K+, force could be restored almost completely within 5-10 min by the addition of salbutamol or adrenaline and partly by insulin. 3. In muscles exposed to 12.5 mM K+, force declined by 96%. Salbutamol (10(-5) M), adrenaline (10(-6) M) and insulin (100 mU ml-1) produced 57-71, 61-71 and 38-47% recovery of force within 10-20 min, respectively. The effects of these supramaximal concentrations of salbutamol and insulin on force recovery were additive. Salbutamol and adrenaline produced significant recovery of contractility at concentrations down to 10(-8) M (P < 0.005). 4. In soleus, the same agents stimulated 86Rb+ uptake and decreased intracellular Na+. These actions reflect stimulation of active Na(+)-K+ transport and both showed a highly significant correlation to the recovery of twitch as well as tetanic force (r = 0.80-0.88; P < 0.001). 5. The force recovery induced by salbutamol, adrenaline and insulin was suppressed by pre-exposure to ouabain (10(-5) M for 10 min or 10(-3) M for 1 min) as well as by tetrodotoxin (10(-6) M). 6. The observations support the conclusion that the inhibitory effect of high [K+]o on contractility in skeletal muscle can be counterbalanced by stimulation of active electrogenic Na(+)-K+ transport, the ensuing increase in the clearance of extracellular K+ and in the transmembrane electrochemical gradient for Na+.