Oxygen free radicals mediate potentiation of the GABA rho1 receptor function by H2O2

ANDREA BELTRÁN GONZÁLEZ; JAVIER GASULLA; DANIEL J. CALVO

Huerta Grande. Córdoba

Congreso; XXVII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2012

Sociedad Argentina de Investigación en Neurociencias

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 diffusible messengers for neuron-glia signaling. Increased production of ROS produces oxidative stress and damage to the central nervous system, as seen in normal aging and neurodegenerative disorders. Diverse neurotransmission systems are modulated by ROS, including the adrenergic, dopaminergic, serotonergic and GABAergic. We previously demonstrated that H2O2 potentiates homomeric rho1 GABA receptor (GABArho1R) function trough the intracellular Cys-364. Now we analyzed 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). GABArho1R were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents electrophysiologically recorded in the presence of H2O2 and modulators of the OH. concentration. Lipoic acid (free radicals scavenger) or deferoxamine (iron chelator) prevented H2O2 potentiation whereas pre-incubation with FeSO4 enhanced it. These results suggest that oxygen free radicals mediate the potentiation of the GABArho1R function by H2O2.