Conclusion

This study identifies that acute EtOH exposure (0.1% at an early stage of synapse development, at E11) suggested a reduction in GABA uptake in the embryonic chicken retina without changing total GAT-1 abundance. The effect is reversible and is associated with the involvement of PKA and PKC signaling pathways, suggesting that a post-translational regulation may contribute to reduced transporter function rather than expression. Because GABA transport is already active at E11 and increases by E16, the acute EtOH-induced modulation of GABA clearance observed in the present study may be relevant to retinal circuit establishment. Co-application with NO-711 further lowers uptake, consistent with GAT-1 representing a major contributor to the EtOH-sensitive component of GABA uptake, while not excluding roles for other high-affinity GABA transporters. The combination of reversibility, kinase dependence, and unchanged protein levels is consistent with dynamic control of transporter activity through mechanisms that may involve phosphorylation and/or membrane trafficking as a plausible mechanism. Future studies should unravel the molecular steps linking acute EtOH to GAT-1 control (e.g., signaling, surface trafficking kinetics, transporter interactors) and test whether similar rules apply at other developmental stages and for other GABA transporter isoforms.