Inhibitory effect of Cd2+ on glycine-induced chloride current in rat hippocampal neurons

The effects of cadmium (Cd2+) on glycine-induced Cl- current (I-Gly) were investigated in acutely dissociated rat hippocampal CA1 neurons using the conventional whole-cell patch-clamp technique in this study. We found that Cd2+ reversibly and concentration-dependently, reduced the amplitudes of I-Gly, with an IC50 of 1.27 mM and Hill coefficient of 0.45. The depression of I-Gly by Cd2+ was independent of membrane voltage between -60 and +40 mV and did not involve a shift in the reversal potential of the current. A non-competitive inhibition was suggested by a double reciprocal plot of the effects of Cd2+ on the concentration-response curve of the I-Gly. Since intracellular dialysis with 3 mM Cd2+ failed to modify I-Gly, it was suggested that the site of action of Cd2+ is extracellular. The suppression of I-Gly by Zn2+ was unaffected by 3 mM Cd2+, which indicated that Zn2+ and Cd2+ bind to independent sites on glycine receptor. The results show that Cd2+ decreases I-Gly in acutely dissociated rat hippocampal neurons and the depression of I-Gly by Cd2+ may contribute to worsen the neurotoxicological impairment. (c) 2006 Elsevier Inc. All rights reserved.