INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
artículos
Título:
Redox modulation of homomeric rho1 GABAC receptors
Autor/es:
CALERO CECILIA I; CALVO DANIEL J
Revista:
JOURNAL OF NEUROCHEMISTRY
Editorial:
Blackwell Sinergy
Referencias:
Año: 2008 vol. 106 p. 2367 - 2374
ISSN:
0022-3042
Resumen:
The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABAa receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABAc receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABArho receptors expressed in Xenopus laevis oocytes. The reducing agents dithiothreitol (2 mM) and N-acetyl-L-cysteine (1 mM) potentiated GABA-evoked Cl-) currents recorded by two-electrode voltage-clamp, while the oxidants 5-5´-dithiobis-2-nitrobenzoic acid (500 microM) and oxidized dithiothreitol (2 mM) caused inhibition. The endogenous antioxidant glutathione (5 mM) also enhanced GABArho1 receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABArho1 receptors was strongly dependent on the GABA concentration; dose–response curves for GABA were shifted to the left in the presence of reducing agents, whereas oxidizing agents produced the opposite effect, without changes in the maximal response to GABA and in the Hill coefficient. Our results demonstrate that, similarly to GABAa receptors and other members of the cys-loop receptor superfamily, GABAc receptors are subjected to redox modulation. Keywords: antioxidants, chloride currents, cys-loop receptors, GABAc receptors, redox modulation, retina.