Cu2+ suppresses GABA(A) receptor-mediated responses in rat sacral dorsal commissural neurons.
The effect of copper ions (Cu(2+)) on gamma-aminobutyric acid (GABA)-induced responses in acutely dissociated neurons from the rat sacral dorsal commissural nucleus (SDCN) was investigated using a nystatin-perforated patch recording configuration under voltage clamp conditions. The application of Cu(2+) to SDCN neurons reversibly suppressed the GABA (10 microM)-activated Cl(-) current (I(GABA)) in a concentration-dependent manner (1-1000 microM; IC(50) = 24.5 microM). In the presence of Cu(2+) (30 microM), the concentration-response curve of GABA was shifted rightward without reducing I(GABA) recorded under the maximally effective concentration of GABA, thus indicating a dependence of Cu(2+) action on GABA concentration. Inhibition of GABA (10 microM) responses by 30 microM Cu(2+) was essentially voltage independent and was not accompanied by a shift in the reversal potential of the currents. Cu(2+) antagonized the suppressive effect of Zn(2+) in a concentration-dependent manner, suggesting competition between Cu(2+) and Zn(2+) for similar binding sites. These data demonstrate that Cu(2+) is a potent inhibitor of GABA(A) receptor-mediated responses, implying a possible modulatory effect of Cu(2+) on GABAergic synaptic transmission in the mammalian SDCN.
Zhu
Hai-Lei
HL
Department of Anatomy and KK Leung Brain Research Centre, Fourth Military Medical University, Xi'an, China.
Wang
Dian-Shi
DS
Li
Ji-Shuo
JS
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012447:Sacrum; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D003300:Copper; D015032:Zinc