GABA受体对谷氨酸受体的调控机制研究

Mechanism of GABA receptors modulating glutamate receptors

目的研究γ-氨基丁酸(GABA)受体对离子型谷氨酸受体的调控机制。方法采用细胞膜片钳电生理技术,以GABA、谷氨酸(Glu)刺激记录GABA受体及Glu受体离子通道介导的全细胞电流(IGABA,IGlu),观察GABA对谷氨酸受体离子通道活性的调控;并以荷包牡丹碱(Bic)抑制IGABA、以SO24-或葡萄糖酸根(gluconate-)代替Cl-,研究其抑制作用的分子机制。结果相同浓度GABA与Glu共给药诱导IGABA+Glu较单独给药诱导电流IGABA与IGlu之和小,该差异随浓度升高而降低;不同浓度GABA对Glu30μmol/L诱导电流IGlu抑制作用随GABA浓度升高而增强,该抑制作用可以被Bic、SO24-与gluconate-消除。结论 GABAA受体能抑制谷氨酸受体介导的全细胞电流,该作用具有浓度依赖性,其抑制机制可能与Cl-的通透性有关。

Objective To investigate the mechanism of γ-aminobutyric acid（GABA）receptors modulating glutamate receptors.Methods Whole-cell patch-clamp recording was used to detect GABA and glutamate receptors-mediated whole-cell currents（IGABA,IGlu）in cultured rat hippocampal neurons.The molecular mechanism of GABA receptors modulating glutamate receptors was studied,using bicuculline（Bic）to inhibit IGABA,and SO2-4 or gluconate-to replace Cl-.Results Co-application of GABA and glutamate-induced IGABA＋Glu was less than expected summation of currents IGABA and IGlu,which were induced by application of GABA and glutamate respectively,and the difference was reduced with the increase of concentrations.GABA rapidly and reversibly inhibited IGlu activated by 30 μmol/L of glutamate in a concentration-dependent manner.And the inhibition could be reversed by bicuculline,SO2-4 and gluconate-.Conclusion GABAA receptors can down-regulate glutamate receptors,and the mechanism may be related to Cl--permeability.