INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Nitric oxide enhances homomeric rho1 GABAc receptor function
Autor/es:
J GASULLA AND DJ. CALVO
Lugar:
San Diego
Reunión:
Congreso; Society for Neuroscience 40th Annual Meeting; 2010
Institución organizadora:
Society for Neuroscience
Resumen:
Nitric oxide (NO) is a diffusible gas produced in the central nervous system by the neural nitric oxide synthase (nNOS). Several neurotransmitter receptors and voltage-gated channels can be modulated by NO by s-nitrosylation of one or more cysteines. Nitrogen reactive species have been involved in the regulation of inhibitory gabaergic neurotransmission. NO was shown to increase the frecuency of spontaneous and miniature inhibitory postsynaptic currents mediated by GABAA receptors in hippocampal, thalamic and hypothalamic neurons (Zanelli, Brain Res, 2009; Yang, J Neurophysiol, 2007; Li, J Neurophysiol, 2002). Past work demonstrated that homomeric ñ1 GABAC receptors (GABAñ1R) can be modulated by reducing and oxidizing agents acting on extracellular cysteines forming the cys-loop (Calero, J Neurochem, 2008). Based on these data, we examined if NO could also modulate GABAñ1R activity. Human GABAñ1R were expressed in Xenopus laevis oocytes and GABA-evoked responses (chloride currents) recorded by two-electrode voltage clamp in the presence or absence of the NO donor 1,1-diethyl-2-hydroxy-2-nitroso-hydrazine sodium (DEA/NO). DEA/NO applications (100ìM) significantly enhanced GABAñ1R-mediated responses. DEA/NO-induced potentiation of the ionic currents elicited by low concentrations of GABA (0.3ìM) was +60.4±18.6% (n=14) and effects were fast and reversible. Meanwhile, DEA/NO also increased current maximal values in a +9.8±2.9 % (n=8) and this effects were only partially washed out. The co-application of the specific NO scavenger 2-(4-carboxyphenyl)-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide potassium salt (CPTIO) (100 mM) and DEA/NO completely prevented potentiation of currents evoked by 0.3ìM GABA, indicating that this modulation is due to a genuine action of NO. Our results demonstrate that GABAC receptors can be modulated by nitrogen reactive species, particularly by NO. The fast and reversible character of NO potentiation at low GABA concentrations suggests that at least part of NO effects could be produced directly on the ñ1 receptor subunits, possibly by s-nitrosylation of cysteines.