Cu(2+) inhibition of glycine-activated currents in rat sacral dorsal commissural neurons.
The effect of Cu(2+) on glycine (Gly) response was examined in neurons acutely dissociated from the rat sacral dorsal commissural nucleus (SDCN) using the nystatin perforated patch clamp recording configuration under voltage-clamp conditions. Cu(2+), in the concentration range 10-1000 microM, reversibly inhibited chloride current activated by 30 microM Gly at a holding potential of -40 mV with an IC(50) of 88.4 microM. Cu(2+) shifted the Gly concentration response curve to the right in a parallel manner, which indicated that Cu(2+) decreased the apparent affinity of the receptor for Gly. Cu(2+) suppression of Gly-activated current was independent of membrane potential between -60 and +60 mV and did not involve a shift in the reversal potential of the current. Furthermore, Cu(2+) antagonized the inhibitory action of Zn(2+) in a concentration-dependent manner, suggesting a common site or mechanism of action of Cu(2+) and Zn(2+) on Gly receptors. The results show that Cu(2+) is a potent inhibitor of Gly receptor-mediated responses in rat spinal neurons.
Wang
Dian-Shi
DS
Department of Anatomy and K. K. Leung Brain Research Centre, Fourth Military Medical University, Xi'an 710032, China. dianshiw@yahoo.com
Zhu
Hai-Lei
HL
Hong
Zhen
Z
Li
Ji-Shuo
JS
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000378:metabolism* / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D007477:Ions / Q000378:metabolism / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism*; D012447:Sacrum; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology
D007473:Ion Channels; D007477:Ions; D018009:Receptors, Glycine; D003300:Copper; D015032:Zinc; D005998:Glycine