异丙酚对大鼠海马神经元高电压激活钙电流的影响

Effect of propofol on high-voltage-activated calcium currents in rat hippocampal neurons

目的 探讨异丙酚对大鼠海马神经元高电压激活钙电流[Ica（HVA）]的影响.方法 原代培养Wistar大鼠海马神经元,采用全细胞膜片钳技术测定Ica（HVA）.记录不同浓度（3、10、30、100、300 μmol/L）异丙酚下Ica（HVA）的峰电流密度,计算Ica（HVA）抑制率,并绘制异丙酚的浓度-效应曲线,计算半数抑制浓度（IC50）和Hill系数.并记录20 μmol/L异丙酚对Ica（HVA）激活和失活动力学的影响.结果 异丙酚3 μmol/L给药前、后Ica（HVA）峰电流密度差异无统计学意义（P＞0.05）;10、30、100、300 μmol/L异丙酚对Ica（HVA）峰电流密度抑制率分别为（24±6）%、（33±5）%、（36±7）%、（38±3）%.与给药前相比,异丙酚呈浓度依赖性地抑制Ica（HVA）峰电流密度（P＜0.05）.IC50为3.8 μmol/L,Hill系数为0.35.给药前、后最大激活膜电位为（4.0±2.0）mV和（3.8±1.6）mV,半数失活电压为（-32±5）mV和（-35±4）mV,斜率因子为31±5和35±6,给药前、后比较差异均无统计学意义（P＞0.05）.结论 异丙酚可显著抑制大鼠海马神经元Ica（HVA）,异丙酚对中枢神经系统的作用可能与抑制Ica（HVA）有关.

Objective To investigate the effect of propofol on the high-voltage-activated calcium currents [ICa（HVA）] in rat hippocampal neurons. Methods Hippocampal neurons were prepared from Wistar rats and cultured. ICa（HVA） was recorded using whole-cell patch clamp technique. Different concentrations of propofol were added to the culture. The effect of propofol on ICa（HVA） Was evaluated. Results ICa（HVA） was inhibited by propofol in 300 μmol/L reduced peak ICa（HVA） by （24±6）%, （33 ±5） %, （36±7）% and（38±3）% respectively with a mean IC50 of 3.8 μmol/L and Hill coefficient of 0.35. Vmax was shifted from （4.0± 2.0） mV to （3.8 ± 1.6） mV. The V1/2 of inactivation curve was shifted from （- 32 ± 5） mV to （- 35 ± 4） mV and the slope factor was 31 ± 5 and 35 ± 6 before and after administration respectively. Conclusion Propofol produces significant inhibition of calcium currents in the central neurons which may partly explain the action of propofol on central nervous system.