Gaba-stimulated chloride uptake during avian CNS development: modulation by neurosteroids

Abstract

In the present report we studied the GABA-stimulated 36Cl− uptake during chick optic lobe development in order to establish the ontogenetic profile of the functional GABAA receptor complex. A concentration-dependent stimulation of 36Cl− influx by GABA was demonstrated, starting at developmental stages as early as 10 days of incubation. The maximal GABA-induced 36Cl− uptake changed significantly during ontogeny with highest values near hatching. However, GABA potency to stimulate ion influx remained unchanged. We also examined the effect of two neurosteroids, allopregnanolone and epipregnanolone, on GABA-stimulated 36Cl− influx at three developmental stages (embryonic day 14, post-hatching day 1 and adult stage). Both steroids enhanced ion uptake in a concentration-dependent manner, exerting greater stimulatory effects at early developmental stages. Allopregnanolone displayed EC50 values lower than epipregnanolone at all three time points and was also more potent at post-hatching stages. Analysis of the GABA concentration-effect curve disclosed that both steroid decreased EC50 values for GABA stimulation while Emax levels were unaffected. In conclusion, our results showed an early appearance of the GABA-associated chloride channel together with the ability of neurosteroids to modulate GABA-gating of such channel.