Modulation of GABAc receptors by reactive nitrogen compounds

J GASULLA AND DJ. CALVO

Huerta Grande, Cordoba

Congreso; I IRCN, Primera Reunion Conjunta de Neurociencias. Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias; 2009

Sociedad Argentina de Neurociencias y Taller Argentino de Neurociencias

Nitric oxide (NO·) is a difusible gas produced in the central nervous system by neural nitric oxide synthase (nNOS). Different synaptic receptors and ionic channels were demostrated to be modulated by NO· (e.g: NMDA receptor, ryanodine receptor, Ca2+?activated K+ channels, L-type Ca2+ channels, etc) through direct modification of cysteine residues (S-nitrosylation or oxidation to cystine). GABAc receptors have two extracellular and one intracellular cysteines wich are potentially redox sensitive. The aim of the present study is to find out if the activity of GABAc receptors could be regulated by NO·.             Homomeric ñ1 GABAc receptors were expressed in Xenopus laevis oocytes and submaximal GABA-evoked (0,3?1µM) chloride currents were electrophysiological recorded using two-electrode voltage clamp technique in the presence or absence of the NO· donors SNOC (S-nitrosocysteine) (100?500µM) and GSNO (S-nitrosoglutathion) (500?1000µM), both of them can liberate free NO· and transnitrosylate protein sulfhydryl groups. In addition we used DEA/NO (diethylamino nonoate) (100?1000µM) that only behaves as a NO· donor. All the compounds tested reversibly potentiated GABA-evoked currents. Preliminary experiments suggested that the effects induced by reactive nitrogen compounds are dose dependent.             Our results demonstrate that GABAc receptors can be modulated by reactive nitrogen compounds, with NO· as the most probable candidate to exert this modulation.  The mechanisms of action of these agents are currently under study. Supported by FONCyT-CONICET