氟桂利嗪对原代培养大鼠皮质神经元钠离子通道电流的影响  

Effect of flunarizine on Na^+ current in rat cortical neurons after primary culture

作　　者：叶青[1] 陈应柱[1] 陈兰兰[1] 朱艳[1] 武文卉[2] 

机构地区：[1]江苏省苏北人民医院神经内科,扬州225001 [2]江苏省苏北人民医院老年医学科,扬州225001

出　　处：《中华老年心脑血管病杂志》2014年第9期978-981,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：江苏省苏北人民医院科研基金(yzucms201301);"步长杯"江苏省神经病学研究基金(20130725)

摘　　要：目的探讨氟桂利嗪对大鼠皮质神经元电压门控钠离子通道电流的影响及机制。方法选择孕17~18d SD胎鼠培养皮质神经元,应用全细胞记录式膜片钳技术记录神经元钠离子通道电流,先加入0.1、1.0、10.0和100.0μmol/L氟桂利嗪刺激,后续实验使用1μmol/L氟桂利嗪刺激,比较加药前后钠电流相关曲线的变化。结果 0.1、1.0、10.0和100.0μmol/L氟桂利嗪对峰值电流抑制率分别为(14.70±4.39)%,(43.48±3.21)%,(61.91±7.41)%和(77.01±5.80)%,差异有统计学意义(P<0.05),氟桂利嗪达到半数最大抑制率时的药物浓度为0.94μmol/L。与加药前比较,加药后钠电流失活曲线向超极化方向移动了17.03mV;钠通道复活时间常数由(7.51±0.05)ms增至(19.46±0.03)ms,差异有统计学意义(P<0.05);10Hz、50Hz脉冲频率下,加药后钠电流较加药前减少幅度分别为[(21.63±7.36)%至(9.44±5.13)%]和[(45.83±10.04)%至(12.56±6.72)%,P<0.05]。结论氟桂利嗪对皮质神经元钠电流的抑制效应,或能解释其预防偏头痛发作的另一可能机制。Objective To study the effect of flunarizine on voltage-gated Na^＋channel current in rat cortical neurons and its mechanism.Methods Cortical neurons from 17-18 dpregnant SD rats were cultured.Flunarizine（0.1,1.0,10.0,100.0μmol/L）was added into the Na^＋channel current using the whole cell patch clamp technique followed by 1μmol/L.The Na^＋current-associated curves were compared before and after flunarizine was added.Results Flunarizine（at the concentration of 0.1,1.0,10.0,100.0μmol/L）inhibited the Na^＋current in a concentration-dependent manner with an IC50 value of 0.94μmol/L.The shift of Na^＋current inactivation curve to hyperpolarizing direction was 17.03 mV higher after flunarizine was added than before it was added.The Na^＋channel recovery time increased to 19.46±0.03 ms from 7.51±0.05ms（P0.05）.The Na^＋current decreased to 9.44%±5.13%and 12.56%±6.72%after flunarizine was added from 21.63%±7.36%and 45.83%±10.04% before flunarizine was added（P0.05）.Conclusion The inhitory effect of flunarizine on cortical neurons can explain why it can prevent migraine attack.

关 键 词：氟桂利嗪 膜片钳术 钠通道 神经元 偏头痛 大脑皮质 

分 类 号：R747.2[医药卫生—神经病学与精神病学]