Acute hypoxic hypoxia alters GABAA receptor modulation by allopregnanolone and pentobarbital in embryonic chick optic lobe

• Published in: Brain research Vol. 954; no. 2; pp. 294 - 299
• Main Authors: RODRIGUEZ GIL, D. J, MITRIDATE DE NOVARA, A, DE PLAZAS, S. Fiszer
• Format: Journal Article
• Language: English
• Published: London Elsevier 08-11-2002; Amsterdam; New York, NY
• Subjects: Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Fundamental and applied biological sciences. Psychology; Molecular embryology; Embryonic development; Oxygen; Embryo; Acute; Barbiturate; Environmental factor; CNS; Neurosteroid; Pregnanolone; Optic lobe; Vertebrata; Pentobarbital; Hypoxia; Chicken; Aves; GABAA receptor; Gabaergic receptor A
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(02)03357-7

Using a previously developed model of acute normobaric hypoxic hypoxia on chick embryos, here we studied at embryonic day 12 the in vitro effect of two positive allosteric modulators of GABA binding, the barbiturate sodium pentobarbital and the neurosteroid allopregnanolone. In both cases an increase in Emax values in membranes obtained from hypoxic embryos was observed. Studies of GABA-gated chloride influx showed that there were no differences in maximal chloride uptake between hypoxic and control membranes. We have already demonstrated that maximal density of GABA binding sites was decreased after hypoxia, suggesting that each of the remaining GABAA receptors display a greater chloride flux than controls. To further characterize GABAA receptor alterations, GABA-gated chloride influx modulated by the above barbiturate and neurosteroid was determined, finding that Emax values were increased 60% and 42%, respectively. The increase in Cl super(-) influx per receptor subsequent to hypoxic trauma, and the enhancement in the modulatory properties studied, may mediate neuronal damage by potential changes in subunit interaction at the GABAA receptor level.