Redox modulation of homomeric rho1 GABA receptors.
The activity of many receptors and ion channels in the nervous system can be regulated by redox-dependent mechanisms. Native and recombinant GABA(A) receptors are modulated by endogenous and pharmacological redox agents. However, the sensitivity of GABA(C) receptors to redox modulation has not been demonstrated. We studied the actions of different reducing and oxidizing agents on human homomeric GABArho(1) 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 GABArho(1) receptor-mediated currents while its oxidized form GSSG (3 mM) had inhibitory effects. All the effects were rapid and easily reversible. Redox modulation of GABArho(1) 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 GABA(A) receptors and other members of the cys-loop receptor superfamily, GABA(C) receptors are subjected to redox modulation.
Calero
Cecilia I
CI
Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Exactas y Naturales Universidad de Buenos Aires (UBA), Ciudad Autónoma de Buenos Aires, Argentina.
Calvo
Daniel J
DJ
D000818:Animals; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D018079:Receptors, GABA / Q000502:physiology*; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018079:Receptors, GABA; C523978:rho1 GABA(C) receptor, human; D005680:gamma-Aminobutyric Acid; D004228:Dithionitrobenzoic Acid