Effects of cadmium on quantal transmitter release and ultrastructure of frog motor nerve endings

Exposure of frog cutaneous pectoris nerve-muscle preparations to cadmium (0.1-1 mM) results in an increase in miniature end-plate potential (m.e.p.p.) frequency. The increase is dependent on the concentration, the time of exposure and the co-presence of other divalent cations in the extracellular fluid. The stimulatory effect of cadmium is most marked in a calcium-free medium. Increased levels of calcium (4-10 mM) or of magnesium (10 mM) reduce the stimulatory effect suggesting that those cations interfere with the entry of cadmium into nerve endings. Once the effect of cadmium on m.e.p.p. frequency is attained, washing with a cadmium-free solution fails to abolish its effect. The action of cadmium on m.e.p.p. frequency slowly declines towards zero after about 3 hrs. An ultrastructural study of nerve terminals exposed for one hr to 1 mM cadmium reveals that neither in calcium-containing nor in a nominally calcium-free medium are there any significant changes in the number of synaptic vesicles as compared to controls. However, after 3 hrs of cadmium action in a calcium-free medium there is about 65% depletion of synaptic vesicles, while in calcium-containing media there is only about 25% depletion. The results suggest that cadmium by itself can support transmitter release but not synaptic vesicle recycling which instead might depend upon calcium.