Effects of sulfhydryl agents on neuromuscular transmission in the presence or absence of cadmium.

To test whether thiol groups are involved in neuromuscular transmission and its blockade by cadmium, the influence of sulfhydryl reagents were investigated on neuromuscular transmission, in the presence or absence of cadmium, using isolated mouse phrenic nerve-diaphragm muscles. Cadmium attenuated twitches evoked by indirect shocks but had almost no effect on twitches by direct shocks in the presence of d-tubocurarine (2.5 microM). The inhibitory effect was reversed by cysteine or by an increase in external calcium. The sulfhydryl oxidizing agent DTNB 5,5'-dithiobis(2-nitrobenzoic acid) potentiated the inhibitory effect of cadmium. Conversely, the reducing agent dithiothreitol (DTT) inhibited this effect. The potentiation by DTNB could be reversed by subsequent application of DTT. The sulfhydryl reagents had no influence on neuromuscular transmission in the absence of cadmium. Neuromuscular transmission was inhibited by the removal of calcium. This inhibition could be reversed by readmission of calcium. This restoration was neither potentiated nor reduced in the presence of these sulfhydryl reagents: It is suggested that an interaction of cadmium with thiol groups is independent of its calcium antagonistic action on neuromuscular transmission. Thiol groups may protect the transmission from the effect of cadmium.