Modulatory action of zinc on GABA(A) receptor complex during avian CNS development.
In the present work, we studied the effect of zinc on GABA(A) receptor complex at three developmental stages of chick optic lobe (embryonic day 14, post-hatching 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 microM 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(max)) from 7. 53 +/- 1.06 pmol/mg protein to 4.63 +/- 0.53 pmol/mg protein, in the absence and presence of 100 microM zinc, respectively, while the dissociation constant (K(d)) remained unchanged. Analysis of the GABA concentration-effect curve at the embryonic stage revealed that the addition of 100 microM zinc decreased E(max) values for GABA stimulation of chloride uptake from 26.46 +/- 2.64% to 16.40 +/- 1. 96%, while EC(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.
Gravielle
M C
MC
Institute of Cell Biology, Prof. E. De Robertis School of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
de Novara
A M
AM
de Plazas
S F
SF
D000818:Animals; D002642:Chick Embryo / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology*; D016015:Logistic Models; D009899:Optic Lobe, Nonmammalian / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects*; D012044:Regression Analysis; D015032:Zinc / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D002712:Chlorides; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D015032:Zinc