Abstract
1. Depolarization caused by carbachol or decamethonium is followed by spontaneous recovery of membrane potential in the presence of the drug. The involvement of the Na pump in this recovery has been investigated in guinea-pig diaphragm at 37 degrees C. 2. Restoration of potassium ions (K+) to the bathing solution gives a rapid recovery of membrane potential which is compatible with a component of recovery of potential being attributable to an electrogenic ion pump and from which a Na pump current of over 60 nA has been estimated. 3. The maintenance of membrane potential in the presence of depolarizing drugs is interpreted in terms of a residual rate of channel opening at a time when the membrane potential is restored, balanced by Na pump action producing tubular depletion of K+. To account for these results a Na pump conductance has been added to a model circuit of drug action. 4. The peak end-plate current produced by carbachol (80 microM) is 100 nA (n = 11) as recorded by the voltage clamp technique; similar estimates may be obtained from measurements of input resistance which falls to 31% of the initial value (n = 5). In muscles desensitized by carbachol for 30 min the end-plate current is 11 nA. 5. In normal muscle removal of K+ from the bathing solution produces a reversible hyperpolarization. In muscles where the membrane potential has recovered in the continued presence of the drug, a hyperpolarization is also found on removal of K+. Withdrawal of K+ during the early stage of spontaneous recovery of potential produces a depolarization or an arrest of the spontaneous repolarization. These results are interpreted in terms of the Na pump producing different effects during the course of spontaneous repolarization. 6. Indirect evidence for K+ depletion in the transverse tubules by the Na pump is provided by an increased resistance to inward current following brief exposure to carbachol or decamethonium. A similar mechanism is used to interpret both the observed change in end-plate revérsal potential to a more negative value and the marked diminution in the amplitude of the action potential at the end-plate during drug action.