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.
J Neurochem. 2008 Jun 1;105(6):2367-74. doi: 10.1111/j.1471-4159.2008.05319.x.
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.
许多神经系统中的受体和离子通道的活性可以通过氧化还原依赖的机制来调节。天然和重组的 GABA(A) 受体受内源性和药理学氧化还原剂的调节。然而，GABA(C) 受体对氧化还原调节的敏感性尚未得到证明。我们研究了不同还原和氧化试剂对在非洲爪蟾卵母细胞中表达的人同源 GABA Rho(1) 受体的作用。还原剂二硫苏糖醇（2 mM）和 N-乙酰-L-半胱氨酸（1 mM）增强了双电极电压钳记录的 GABA 诱导的 Cl(-) 电流，而氧化剂 5-5'-二硫代双-2-硝基苯甲酸（500 microM）和氧化的二硫苏糖醇（2 mM）则引起抑制。内源性抗氧化剂谷胱甘肽（5 mM）也增强了 GABA Rho(1) 受体介导的电流，而其氧化形式 GSSG（3 mM）则具有抑制作用。所有的作用都是快速和容易逆转的。GABArho(1) 受体的氧化还原调节强烈依赖于 GABA 的浓度；在还原剂存在的情况下，GABA 的剂量反应曲线向左移动，而氧化剂则产生相反的效果，对 GABA 的最大反应和 Hill 系数没有变化。我们的结果表明，类似于 GABA(A) 受体和 cys 环受体超家族的其他成员，GABA(C) 受体也受到氧化还原调节。
