Modulation of GABAc receptors by reactive oxygen species

A BELTRAN GONZALEZ AND DANIEL J. CALVO

Congreso; II RCN, Segunda Reunion Conjunta de Neurociencias. Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias; 2010

Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias

Reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), hydroxyl radical (OH.) and superoxide anion (O2-.) are generated as by products of the cellular oxidative metabolism and secondary to the activation of NMDA and AMPA receptors. ROS have been implicated in normal aging and in neurodegenerative disorders including Parkinson and Alzheimer’s disease, amyotrophic lateral sclerosis and ischemia-reperfusion injury. Numerous neurotransmitter systems are modulated by ROS, including dopaminergic, serotonergic, adrenergic and GABAergic receptors. Even though ROS effects on GABAA receptor-mediated synaptic transmission has been reported, the modulation of GABAC receptors by these species has not been determined. The aim of the present study was to analyze if GABAC receptors can be regulated by ROS. Homomeric GABAñ1 receptors (GABAñ1-R) were expressed in Xenopus laevis oocytes and GABA-evoked (0.3–1 µM) chloride currents were recorded by two-electrode voltage-clamp in the presence or absence of H2O2 (1 mM). Preliminary results showed that the application of H2O2 significantly potentiated GABA-evoked currents. H2O2 effects were reversibly, voltage independent and strongly depended on GABA concentration. These results suggest that GABAC receptors can be modulated by ROS. The mechanisms of action are currently under study.