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

The effects of cadmium (Cd(2+)) 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 Cd(2+) reversibly and concentration-dependently, reduced the amplitudes of I(Gly), with an IC(50) of 1.27 mM and Hill coefficient of 0.45. The depression of I(Gly) by Cd(2+) 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 Cd(2+) on the concentration-response curve of the I(Gly). Since intracellular dialysis with 3mM Cd(2+) failed to modify I(Gly), it was suggested that the site of action of Cd(2+) is extracellular. The suppression of I(Gly) by Zn(2+) was unaffected by 3mM Cd(2+), which indicated that Zn(2+) and Cd(2+) bind to independent sites on glycine receptor. The results show that Cd(2+) decreases I(Gly) in acutely dissociated rat hippocampal neurons and the depression of I(Gly) by Cd(2+) may contribute to worsen the neurotoxicological impairment.