Acute hypoxic hypoxia alters GABA(A) receptor modulation by allopregnanolone and pentobarbital in embryonic chick optic lobe.
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 E(max) 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 GABA(A) receptors display a greater chloride flux than controls. To further characterize GABA(A) receptor alterations, GABA-gated chloride influx modulated by the above barbiturate and neurosteroid was determined, finding that E(max) values were increased 60% and 42%, respectively. The increase in Cl(-) 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 GABA(A) receptor level.
Rodríguez Gil
D J
DJ
Instituto de Biología Celular y Neurociencias, Professor E De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, 1121 Buenos Aires, Argentina.
Mitridate de Novara
A
A
Fiszer de Plazas
S
S
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D018757:GABA Modulators / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009899:Optic Lobe, Nonmammalian / Q000187:drug effects / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*
D000777:Anesthetics; D018757:GABA Modulators; D011963:Receptors, GABA-A; D011280:Pregnanolone; D010424:Pentobarbital