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".
Molnár
Gábor
G
Department of Experimental Zoology, Balaton Limnological Research Institute, HAS, Tihany, Klebelsberg K. u. 3, P.O. Box 35, H-8237, Hungary. molnarg@tres.blki.hu
Salánki
János
J
Kiss
Tibor
T
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D018756:GABA Antagonists; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D008195:Lymnaea / Q000502:physiology*; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000697:Central Nervous System Stimulants; D018118:Chloride Channels; D018756:GABA Antagonists; D007473:Ion Channels; D002104:Cadmium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002110:Caffeine; D005680:gamma-Aminobutyric Acid; D013498:Suramin; D037342:Pertussis Toxin; D002118:Calcium