MODE OF ACTION OF TETANUS TOXIN ON THE NEUROMUSCULAR JUNCTION

Studies on the source of the activated spontaneous discharge of miniature end-plate potentials MEPPs by tetanus toxin indicate that the MEPPs are those whose release mechanism is both calcium- and voltage-dependent. The potentiation of spontaneous release by toxin did not occur in the absence of calcium or magnesium it was enhanced by increasing the calcium concentration. These results, together with the observation that depolarization by potassium blocked or reversed the peripheral effect of tetanus toxin, suggest that the toxin acts by lowering the presynaptic resting membrane potential. Studies of the direct effect of toxin on neuromuscular transmission in the rat phrenic nerve-diaphragm preparation indicate that the toxin decreases the probability of transmitter release by a nerve spke, the rate of initial transmitter depletion, and the level of sustained transmitter output.