Modulatory Action of Zinc on GABA sub(A) Receptor Complex During Avian CNS Development

• Published in: Journal of neuroscience research 1999-08, Vol.57 (4), p.536-540
• Main Authors: Gravielle, M C, de Novara, AM, de Plazas, SF
• Format: Article
• Language: English
• ISSN: 0360-4012
• DOI: 10.1002/(SICI)1097-4547(19990815)57:4<536::AID-JNR13>3.3.CO;2-P

In the present work, we studied the effect of zinc on GABA sub(A) receptor complex at three developmental stages of chick optic lobe (embryonic day 14, posthatching day 1, and adulthood), in order to investigate the role of this cation in central nervous system (CNS) functional maturation. It was demonstrated that zinc exerts an inhibitory modulation of both GABA binding and GABA-gated chloride flux in a concentration-dependent manner with maximal effects at 100 mu M zinc concentration. Maximal inhibition was higher at the embryonic stage and declined thereafter, disclosing minimal values at the adult stage. The effect of zinc on saturation GABA binding experiments performed at embryonic day 14 demonstrated that the cation decreased the maximal number of binding sites (B sub(max)) from 7.53 plus or minus 1.06 pmol/mg protein to 4.63 plus or minus 0.53 pmol/mg protein, in the absence and presence of 100 mu M zinc, respectively, while the dissociation constant (K sub(d)) remained unchanged. Analysis of the GABA concentration-effect curve at the embryonic stage revealed that the addition of 100 mu M zinc decreased E sub(max) values for GABA stimulation of chloride uptake from 26.46 plus or minus 2.64% to 16.40 plus or minus 1.96%, while EC sub(50) values were unaffected. In conclusion, our results suggest that zinc acts as a non-competitive inhibitor of both GABA binding and GABA responses during avian CNS development, with its effect inversely related to age.