Effects of vinblastine in the frog neuromuscular junction during repetitive stimulation

Vinblastine (10(-5) to 10(-4) M) applied in a Mg-blocked sciatic nerve-sartorius muscle preparation of the frog at the beginning of 20 min of repetitive stimulation of the nerve at 10 Hz, markedly inhibited the facilitation period. There was a smaller increase of end-plate potential amplitude, of quantal content, and of miniature end-plate potential (MEPP) frequency in comparison with that found in experiments without the drug. This depressant effect was more evident when the preparation was preincubated in vinblastine: synaptic responses often disappeared after a few minutes, whereas MEPP frequency attained a maximum at the 5th min. The results suggest a multiple site of action for vinblastine. First, an alteration of both vesicle and plasmalemma membrane, as revealed by the increase of MEPP frequency and by the change of the binomial release features. Second, the drug could damage the intracellular transport system, interfering with the mobilization of the vesicles toward the nerve endings, as shown by the very low or absent facilitation.