国际麻醉学与复苏杂志   2013, Issue (2): 1-1
    
氯胺酮对大鼠海马神经元低电压激活钙电流的抑制作用
林思芳, 谭宏宇, 叶铁虎1()
1.中日友好医院麻醉科
Suppressive effect of ketamine on low-voltage-activated calcium currents in rat hippocampal neurons
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摘要:

目的 探讨氯胺酮对大鼠海马神经元低电压激活钙电流[low-voltage-activated calcium currents, ICa(LVA)]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(LVA)。记录不同浓度(10、30、100、300、1 000 μmol/L)氯胺酮下ICa(LVA)的峰电流密度,计算ICa(LVA)抑制率,并绘制氯胺酮的浓度-效应曲线,计算半数抑制浓度(IC50)和Hill系数。并记录100 μmol/L氯胺酮对ICa(LVA)激活和失活动力学的影响。 结果 氯胺酮10 μmol/L给药前、后ICa(LVA)峰电流密度差异无统计学意义(P>0.05);30、100、300、1 000 μmol/L氯胺酮对ICa(LVA)峰电流密度抑制率分别为(12±4)%、(19±4)%、(32±3)%、(31±2)%。与给药前比较,氯胺酮呈浓度依赖性地抑制ICa(LVA)峰电流密度(P<0.05)。IC50为110 μmol/L,Hill系数为0.14。给药前、后半数最大激活膜电位分别为(-8±0) mV 和 (-10±2) mV,斜率因子κ分别为(7±0)和(8±1);半数最大失活电压为(-42±6) mV和(-48±6) mV,κ分别为(22±5)和(27±7),给药前、后比较,差异均无统计学意义(P>0.05)。 结论 氯胺酮可显著抑制大鼠海马神经元ICa(LVA),氯胺酮对中枢神经系统的作用可能与抑制ICa(LVA)有关。

关键词: 氯胺酮;海马;膜片钳;钙通道
Abstract:

Objective To investigate the effect of ketamine on the low-voltage-activated calcium currents [ICa(LVA)]in rat hippocampal neurons. Methods Hippocampal neurons were isolated from Wistar rats and cultured. ICa(LVA) was recorded using whole-cell patch clamp technique. Different concentrations of ketamine were added to the culture. The effect of ketamine on ICa(LVA) was evaluated. Results ICa(LVA) was inhibited by ketamine in a concentration-dependent manner. Ketamine at the concentration of 10 μmol /L had no effect on ICa(LVA). Ketamine at the concentration of 30, 100, 300 μmol/L and 1 000 μmol/L reduced peak ICa(LVA) by(12±4)%, (19±4)%, (32±3)%, (31±2)% respectively. The IC50 was at 110 μmol/L and Hill coefficient was 0.14. V1/2 of activation curve was shifted from (-8±0) mV to (-10±2) mV. The V1/2 of inactivation curve was shifted from (-42±6) mV to (-48±6) mV. Conclusions Ketamine produces significant inhibition of ICa(LVA) in hippocampal neurons which may partly explain the action of ketamine on central nervous system.

Key words: Ketamine; Hippocampus; Patch clamp; Calcium channels