Cellular and Molecular Neurobiology
Author: Manuel Ignacio López Pazos | email: manupazos89@gmail.com
Manuel Ignacio López Pazos 1°, Mariana del Vas 2°, Andrea Nora Beltrán González 1°, Daniel Juan Calvo 1°
1° Laboratorio de Neurobiología Celular y Molecular. IFIByNE-UBA-CONICET
2° Instituto de Biotecnología, CICVyA, INTA
Reactive oxygen species (ROS) were involved in neuronal signalling and plasticity in normal physiology, aging and neurodegenerative disorders. Besides, GABAergic neurotransmission is sensitive to redox agents, including ROS. We previously reported the modulation of tonic responses mediated by GABAA?1 receptors by hydrogen peroxide (H2O2) through thiol modification of cysteines. We also showed that endogenous redox agents modulate phasic GABAA receptor subtypes, but diverse molecular mechanisms of action appear to underlie these effects. We characterized H2O2 effects on different GABAA receptor subtypes by expression in Xenopus laevis oocytes followed by electrophysiological recording. In the presence of H2O2 (1mM) responses mediated by receptors containing ?? and ??? subunits were potentiated, while the presence of the ?2 subunit conferred resistance to ROS modulation. H2O2 effects on GABAA?1?2 responses were reversible, dose and use-dependent, voltage-insensitive and partially prevented by irreversible alkylation of sulfhydryl groups with NEM. Increases in agonist concentration partially reduced effects exerted by H2O2. Concentration-response curves in the presence of H2O2 showed a leftward shift, compared to control values, and an increase in the maximal response. Further experiments will help to describe the actual mechanisms of action underlying the effects of H2O2 on the different GABAA receptor subtypes. Supported by ANPCyT and CONICET