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.
Wang
Shu
S
School of Life Science and Institute of Polar Environment, University of Science & Technology of China, Hefei, Anhui 230027, PR China.
Gu
Yan
Y
Wang
Hui-Li
HL
Li
Xin-Mei
XM
Wang
Ming
M
Sun
Li-Guang
LG
Ruan
Di-Yun
DY
D000818:Animals; D000831:Animals, Newborn; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005998:Glycine / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D016014:Linear Models; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018118:Chloride Channels; D002104:Cadmium; D005998:Glycine