琥珀酸对大鼠海马CA1区神经元电压依赖性钙电流的影响  

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

作　　者：丛红群[1] 岳旺[1] 

机构地区：[1]青岛大学医学院药理教研室,山东青岛266021

出　　处：《现代生物医学进展》2009年第3期444-447,共4页Progress in Modern Biomedicine

基　　金：国家自然基金项目(No.30572178)

摘　　要：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^(-1)mol·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±17.32 pA,分别给予10^(-6)、10^(-5)、10^(-4)、10^(-3)、10^(-2)和10^(-1) mol·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±3.25 pA,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。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.

关 键 词：琥珀酸 海马神经元 钙电流 膜片钳技术 

分 类 号：R971.6[医药卫生—药品]