Redox modulation of the GABAergic neurotransmission in the retina and the hippocampus.

CALVO DJ

Sierra de la Ventana

Congreso; XLIII Reunión Anual SAB2014; 2014

SAB

y-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system and its actions are mediated by two receptor classes: ionotropic (GABAA) and metabotropic (GABAB). GABAA receptors are ligand-gated chloride channels that belong to the superfamily of ?Cys-loop? receptors which also include the nicotinic acetylcholine, glycine and serotonin 5HT3A receptors. Heteromeric and homomeric GABAA receptor variants can be assembled from a great diversity of subunit subtypes (α1-6, β1-3, γ1-3, δ, ε, θ, π, ρ1-3). Studies from our lab revealed that the extra and intracellular levels of ascorbic acid in the retina regulate the function of tonic (GABAAρ1) and phasic (GABAAα1β2γ2) receptors expressed in bipolar cells. We have also demonstrated that tonic GABAAρ1 receptors are sensitive to endogenous redox agents such as ascorbic acid, glutathione, reactive oxygen species and reactive nitrogen species. The aminoacidic residues which act as targets for redox agents were identified using site directed mutagenesis and receptor expression in oocytes. Preliminary results indicate that responses mediated by tonic and phasic GABAergic receptors in the hippocampus are also subject to redox modulation. Taken together our results suggest that inhibitory neurotransmission mediated by ionotropic GABA receptors is modulated by multiple pathways involving redox signaling.