Modulation of GABAA-rho1 receptors by L-cysteine.

ANDREA N BELTRÁN GONZÁLEZ; FLORENCIA VICENTINI; DANIEL J CALVO

Huerta Grande, Cordoba

Congreso; XXVIV Congreso anual de la Sociedad Argentina de Investigaciones en Neurociencias; 2014

Sociedad Argentina de Investigaciones en Neurociencias

The role of redox mechanisms in the regulation of cell function in the central nervous system has been extensively studied. Many neurotransmitter receptors, including glutamate and GABAA receptors, as well as diverse voltage-gated ion channels and transporters are sensitive to redox modulation. GABAA-rho1 receptors mediate tonic currents elicited by ambient concentrations of GABA in the retina. We have previously demonstrated that GABAA-rho1 receptors responses are potentiated by nitric oxide, glutathione, ascorbic acid and reactive oxygen species through thiol modification of the cysteine residues within the rho1 subunit. Previous reports suggested that the endogenous redox agent L-cysteine modulates calcium channels and induces selective neurotoxicity in the mouse retina, but the effect on GABAA receptors has not been determined yet. In the present study we analyzed the effect of L-cysteine on responses mediated by GABAA-rho1. Homomeric GABAA-rho1 receptors were expressed in Xenopus laevis oocytes and GABA-evoked chloride currents were recorded by two-electrode voltage-clamp in the presence or absence of L-cysteine. L-cysteine inhibited GABAA-rho1 receptors responses. This inhibition was dose-dependent, reversible, voltage independent and depended on GABA concentration. GABAA-rho1 receptor responses were insensitive to L-cystine, the oxidized form of L-cysteine. The mechanism of action of L-cysteine is currently under study.