琥珀酸对大鼠海马CA1区神经元电压依赖性钙电流的影响

目的：观察不同浓度的琥珀酸对大鼠海马CA1区神经元电压依赖性钙通道（voltage—dependent calcium channels，VDCC）电流的作用，初步探讨琥珀酸对神经元保护的电生理学基础。方法：采用传统全细胞膜片钳技术和制霉菌素（nystatin）穿孔膜片钳技术观察琥珀酸对海马CA1区神经元VDCC电流的影响。结果：不同浓度的琥珀酸（10^-6、10^-5、10^-4、10^-3、10^-2和10^-1mol·L^-1）在海马CA1区对低电压激活（low—voltage activated，LVA）钙通道电流未见任何影响，而对高电压激活（high—voltage activated，HVA）钙通道电流的抑制呈浓度依赖性。对照组HVA钙电流为580．05±17．32pA，分别给予10^-6、10^-5、10^-4、10^-3、10^-2和10^-1mol·L^-1。的琥珀酸后，HVA钙电流依次为563．74±16．65，517．99±15．24，444．66±13．26，405．32±19．11，269．03±9．96和86．41±3．25pA，同对照组相比差异有统计学意义（n=8，P〈0．01）。结论：琥珀酸能浓度依赖性地抑制HVA钙电流，而对LVA钙电流无影响。由此推测琥珀酸可能通过抑制HVA钙电流减少Ca^2＋内流而影响海马CA1区神经元的兴奋性，从而抑制癫痫的形成，其脑保护作用可能与此有关。

The Effect of Succinic Acid on the Voltage-dependent Calcium Channel Currents in Rat Hippocampal CA1 Neurons

Objective： To observe the effect of different concentrations of succinic acid on the voltage-dependent calcium channel currents in rat hippocampal CA1 neurons and investigate the electrophysiologic basis of succinic acid＇s protection on neurons. Methods： Traditional whole-cell patch clamp and nystatin-perforated patch clamp techniques were applied to record the voltage-dependent calcium channel currents in the hippoeampal CA1 neurons. Results： Different concentrations of suceinic acid （10^-6、10^-5、10^-4、10^-3、10^-2and10^-1mol·L^-1） inhibited the high-voltage activated calcium currents concentration-dependently in the hippocampal CA1 neurons, but had no ef- fects on the low-voltage activated calcium currents. After different concentrations of succinic acid treatment （10^-6、10^-5、10^-4、10^-3、10^-2and10^-1mol·L^-1） respectively, the high voltage-activated calcium currents decreased from 580.05 ± 17.32 pA in the control group to 563.74 ± 16.65,517.99 ± 15.24, 444.66 ± 13.26, 405.32 ± 19.11 and 269.03 ± 9.96 pA, which was significantly different from that of the control group （n=8, P 〈 0.01）. Conclusions： Succinic acid can inhibit the high-voltage activated calcium currents in a dose-dependent manner, yet it exerts no effects on the low-voltage activated calcium currents. It could be inferred that the anticonvulsive effects of succinic acid may influence the excitability of the hippocampal CA1 neurons via inhibiting the high voltage-activated calcium currents and decreasing the Ca^2＋ influx, so that it could suppress the development of epilepsy. This is probabily related to its protective effects on the brain.