The influence of internal sodium on the behaviour of motor nerve endings

Abstract

Abstract The effects of digoxin at the frog neuromuscular junction were altered by changing the ionic composition of the extracellular fluid, as follows. 1. Sodium-deficient solutions inhibited the increase in e. p. p. amplitude and m. e. p. p. frequency induced by digoxin, and delayed the onset of spontaneous e.p.p. discharges. The time to onset of conduction block in the axon preterminals was shortened in solutions of very low sodium content, but the block could be temporarily reversed by raising the concentration of extracellular sodium. Conduction, after failure in a high-sodium medium, could be restored by prolonged soaking in a solution of very low sodium content. 2. Replacement of chloride by isethionate did not significantly alter the effects of digoxin. 3. Potassium-deficient solutions delayed but did not reduce the effects of digoxin. In these solutions the increase in e. p. p. amplitude, the conduction blockade, and the spontaneous discharge of e. p. ps occurred at lower m. e. p. p. frequencies than in solutions of normal potassium content. Excess potassium reduced the time to conduction blockade and to spontaneous discharge of e. p. ps. 4. Calcium-deficient solutions accelerated the time-course of the effects of digoxin without altering their magnitude. Excess calcium delayed the occurrence of the effects and reduced their magnitude. 5. Magnesium acted like calcium on the time-course of the effects. Excess magnesium enhanced the increase in e. p. p. amplitude produced by digoxin, especially when the calcium concentration was low. Complete replacement of calcium by magnesium did not inhibit the digoxin-induced increase in m. e. p. p. Discharge. It is concluded from these findings that the effects produced by digoxin on motor terminals are generated by the accumulation of intracellular sodium and modified by the loss of intracellular potassium. A mechanism, involving competition with intracellular calcium, is proposed to account for an intracellular action of sodium.