Effects of lindane upon transmitter release and end-plate responsiveness in the neuromuscular junction of the frog.

Studies were carried out to determine whether the insecticide, lindane, influenced calcium-mediated electrical activity or release of neurotransmitter in vitro. In neuroblastoma cells, lindane (1-100 microM) did not appreciably modify action potentials elicited in normal or sodium-free solutions nor did it have a significant effect upon either transient or sustained-type calcium channels. Exposure of cutaneous pectoris neuromuscular junctions of the frog to 100 microM lindane increased spontaneous release of transmitter. In neuromuscular junctions perfused with 0.5 mM Ca++/6 mM Mg++ Ringer (low quantal release conditions), lindane increased evoked release of transmitter. The absolute increase amounted to just less than one quanta and the extent of the increase was inversely proportional to the mean number of quanta released by the nerve terminal before exposure to lindane. No effect on release of transmitter could be demonstrated when neuromuscular junctions were perfused in normal Ringer. Exposure of neuromuscular junctions to 100 microM lindane also decreased the amplitudes of miniature end-plate potentials. Amplitudes of responses to iontophoretically-applied acetylcholine (ACh) were similarly affected, suggesting that the decrease in amplitudes of miniature end-plate potentials was a reflection of decreased sensitivity of the end-plate to ACh. At neuromuscular junctions of the cutaneous pectoris of the frog, lindane appeared to produce two major effects. Presynaptically, it produced changes in spontaneous and evoked release of transmitter that were consistent with a small increase in free intracellular concentration of Ca++. Postsynaptically, it reduced the sensitivity of the end-plate to ACh.