琥珀酸在海马CA1区对突触前GABA释放的影响

Effects of succinic acid on the presynaptic GABA release in hippocampal CA1 field

为了观察琥珀酸在大鼠海马CA1区对突触前GABA释放的影响,我们采用红外可视全细胞膜片钳技术记录了琥珀酸对γ-氨基丁酸(GABA)能自发性微小抑制性突触后电流(miniature inhibitory postsynaptic currents,mIPSCs)的作用。结果显示不同浓度的琥珀酸(10-6mol/L、10-5mol/L、10-4mol/L和10-3mol/L)在海马CA1区均能以浓度依赖的方式增强GABA能mIPSCs的频率,而对其电流幅度没有影响。10-4mol/L琥珀酸组GABA能mIPSCs的频率为2.25±0.99Hz,与正常对照组相比有显著性差异(n=8,P<0.01),而其电流幅度为31.63±6.16pA,与正常对照组相比没有差异(n=8,P>0.05)。以上实验结果表明琥珀酸能通过增强突触前GABA的自发性释放,对海马CA1区神经元产生超极化作用,此作用可能是琥珀酸抑制癫痫形成的主要方式之一。

To determine the effect of succinic acid on the presynaptic GABA release in hippocampal CA1 field, GABAergic spontaneous miniature inhibitory postsynaptic currents （mlPSCs） in the rat hippocampal neurons of the CA1 field were recorded by the infrared visual whole cell patch clamp recording techniques before and after succinic acid administration. The results showed that all of the different concentrations of succinic acid （ 10 ^-6 mol/L, 10^ -5 mol/L, 10^ -4 mol/L and 10^ -3 mol/L） could inhibit the frequency of GABAergic mIPSCs and the inhibitory effect was concentration dependent, while there was no influence of the succinic acid on the range of the current flow. The frequency of GABAergic mlPSCs in the 10^ -4 mol/L succinic acid group was 2.25 ±0.99 Hz, which was significant difference compared with the control group （ n = 8, P 〈 0.01 ）. In the meanwhile, the amplitude of GABAergic mlPSCs in the 10^ -4 mol/L succinic acid group was 31.63 ±6.16 pA, which is no difference compared with the control group （n = 8, P 〉 0. 05 ）. The present results demonstrate that succinic acid has the hyperpolarizing action on the hippocampat CA1 neurons through enhancing the spontaneous presynaptic release of GABA, which might be the main mechanism of succinic acid to inhibit the development of epilepsy.