Redox modulation of homomeric rho(1) GABA(c) receptors.

C.I. CALERO; DANIEL JUAN CALVO

Journal of Neurochemistry

Blackwell Publishig

Lugar: Boston; Año: 2008 vol. 105 p. 2367 - 2374

0022-3042

The activity of many receptors and ion channels in the ner-vous system can be regulated by redox-dependent mecha-nisms. Native and recombinant GABAAreceptors aremodulated by endogenous and pharmacological redoxagents. However, the sensitivity of GABACreceptors to redoxmodulation has not been demonstrated. We studied the ac-tions of different reducing and oxidizing agents on humanhomomeric GABAq1receptors expressed inXenopus laevisoocytes. The reducing agents dithiothreitol (2 mM) andN-acetyl-L-cysteine (1 mM) potentiated GABA-evoked Cl)cur-rents recorded by two-electrode voltage-clamp, while theoxidants 5-5¢-dithiobis-2-nitrobenzoic acid (500lM) and oxi-dized dithiothreitol (2 mM) caused inhibition. The endogenousantioxidant glutathione (5 mM) also enhanced GABAq1receptor-mediated currents while its oxidized form GSSG(3 mM) had inhibitory effects. All the effects were rapid andeasily reversible. Redox modulation of GABAq1receptors wasstrongly dependent on the GABA concentration; dose?re-sponse curves for GABA were shifted to the left in the pres-ence of reducing agents, whereas oxidizing agents producedthe opposite effect, without changes in the maximal responseto GABA and in the Hill coefficient. Our results demonstratethat, similarly to GABAAreceptors and other members of thecys-loop receptor superfamily, GABACreceptors are sub-jected to redox modulation