异丙酚对大鼠脊髓背角神经元河豚毒素敏感型电压门控钠电流的影响

Effect of propofol on TTX-sensitive voltage-gated sodium currents in spinal dorsal horn neurons

目的探讨异丙酚对大鼠脊髓背角神经元河豚毒素敏感型电压门控钠电流的影响。方法出生后1周的SD雄性大鼠,体重12～20g,断头处死,取腰膨大段脊髓（L3～6）,急性分离背角神经元,随机分为6组,对照组背角神经元施加细胞外液,不同浓度异丙酚组于距离神经元100μm处施加0.3、1、3、10、30μmol/L异丙酚,应用全细胞膜片钳记录模式,记录单刺激诱发的钠电流幅度,每组记录14个神经元。计算异丙酚的半数抑制浓度。向神经元施加半数抑制浓度的异丙酚,给予刺激电压-40～30mV,梯度为10mV的连续刺激,记录给药前后不同刺激电压下电流到达峰值的时间,共记录16个神经元。结果与对照组比较,不同浓度异丙酚组钠电流峰值降低（P〈0.05）,异丙酚的半数抑制浓度为（5.35±0.23）μmol/L。施加5.35μmol/L异丙酚后,-30～10mV刺激电压对应电流到达峰值时间较给药前延长（P〈0.05）。结论0.3～30μmol/L异丙酚可抑制大鼠脊髓背角神经元河豚毒素敏感型电压门控钠通道电流,可能与延长钠通道电流到达峰值时间有关。

Objective To investigate the effect of propofol on the amplitude of TTX-sensitive voltage-gated sodium currents and the duration to the maximum amplitude. Methods The spinal cord dorsal horn neurons were prepared from the lumbar enlargement （L3,6） of 7-day-old SD rats and were exposed to 5 different concentrations of propofol 0.3, 1, 3, 10, 30 μmol/L. In control group the neurons were placed in extracellular fluid. Whole-cell patch clamp technique was used to record the sodium currents induced by single stimulus in each group. The IC50 value of propofol was obtained according to Hill equation. The neurons were then exposed to IC50 of propofol. Sodium currents elicited by voltage steps from a holding potential of 80 mV to test potentials varying from - 40 to 30 mV were recorded and the duration from zero to the maximum amplitude of sodium currents were recorded before and after being exposed to IC50 of propofol. Results Sodium currents were significantly decreased when the neurons were exposed to 0.3,1 , 3, 10, 30 μmol/L propofol as compared to the control group （P 〈 0.05） . The IC50 value of propofol was （5.35 ± 0.23） μmol/L, hi the presence of 5.35 μmol/L propofol the duration from zero to maximum amplitude of sodium currents elicited by test potential varying from - 30 mV to 10 mV was significantly increased compared with that beibre exposure to propofol （ P 〈 0,05） . Conclusion Propofol 0.3-30 μmol/L can reduce sodiuln currents in the spinal cord dorsal horn neurons and prolong the duration to maximuln amplitude.