Oxygen free radicals mediate the potentiation of the GABAρ1 receptor function by H2O2.

BELTRÁN GONZALEZ A; GASULLA J; CALVO DJ

Huerta Grande Córdoba

Congreso; XXVII Reunión Nacional Sociedad Argentina de Investigación en Neurociencias (SAN); 2012

Sociedad Argentina de Investigación en Neurociencias

Oxygen free radicals mediate the potentiation of the GABAρ1 receptor function by H2O2. Andrea N. Beltrán González, Javier Gasulla, Daniel J. Calvo. INGEBI-CONICET. In brain cells reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), superoxide anion (O2-.) and hydroxyl radical (OH.), have been implicated as intracellular regulators of neuronal activity and as diffusible messengers for neuron-glia signaling. Increased production of ROS results in oxidative stress and damage to the central nervous system, as seen in normal ageing and neurodegenerative disorders. Diverse neurotransmission systems are modulated by ROS, including the adrenergic, dopaminergic, serotonergic and GABAAergic. However, the modulation of GABAC receptors by these species had not been determined yet. We previously demonstrated that H2O2 significantly potentiates homomeric ρ1 GABA receptor (GABAρ1R) function trough the intracellular Cys-364. In the present study we completed the characterization of the mechanism underlying this modulation. H2O2 could directly oxidize Cys-364 or could act indirectly by the formation of the free radical OH. in the presence of iron (Fenton reaction). GABAρ1R were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents recorded by two-electrode voltage-clamp in the presence of H2O2 and modulators of OH. concentration. The application of lipoic acid (a scavenger of free radicals) and deferoxamine (an iron chelator) decreased the potentiation induced by H2O2, whereas the pre-incubation with FeSO4 increased it. These results suggest that oxygen free radicals mediate the potentiation of the GABAρ1R function by H2O2.