Cadmium inhibits GABA-activated ion currents by increasing intracellular calcium level in snail neurons

Blocking of the GABA-activated chloride current by cadmium was investigated in identified nerve cells (RPeD1, RPaD1) of the pond snail (Lymnaea stagnalis L.), using a two-microelectrode voltage-clamp technique. Cd2+, at 50 microM extracellular concentration, inhibited GABA-activated chloride currents, both in normal and Ca2+-free solution. Intracellular injection of Ca2+ or the application of caffeine mimicked the inhibitory effect of Cd2+ on GABA-elicited currents. Cd2+-block was eliminated, or it was substantially decreased, when neurons were intracellularly loaded with EGTA, or when the Ca2+-release was blocked by ruthenium red. The blocking effect of Cd2+ was also eliminated by applying G-protein inhibitors: pertussis toxin, suramin or GTP-gamma-S. Finally, intracellularly injected Cd2+ was ineffective at eliciting an inward current on GABA-activated currents, suggesting that the Cd2+-binding site resides extracellularly. These results suggest that cadmium inhibited GABA-activated chloride currents by increasing the intracellular Ca2+ level, by releasing it from intracellular stores and by interacting with a putative G-protein-coupled cell-surface "metal-receptor".