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目的:通过观察胍丁胺对大鼠海马神经元电压门控性离子通道的影响来探讨其作用机制。方法:使用膜片箝全细胞记录技术,采用压力注射给药的方法,在培养的新生大鼠海马神经元上观察胍丁胺对其电压门控性钠、钾、钙离子通道的作用。结果:胍丁胺(500 μmol/L)对钠、钾通道(快速失敏钾通道I_A和延迟整流钾通道I_K)没有显著的作用。胍丁胺能抑制钙电流,其抑制作用随浓度增加而加强。在胍丁胺浓度为0.1,0.5,1.5,10.0,50.0和100 μmol/L时,其对电压门控性钙电流的抑制率分别为(21±4)％,(35±6)％ ,(49±6)％,(67±4)％,(69±6)％,(86±8)％和(87±9)％,IC_(50)为1.2±0.4 μmol/L。双因素方差分析显示,细胞膜不同箝制电压水平和不同浓度胍丁胺对钙电流的抑制效应之间存在着明显的交互作用。结论:胍丁胺以浓度依赖性和电压依赖性方式,可逆性地抑制海马神经元电压门控性钙通道,对钙通道的阻断作用可能是胍丁胺产生生理和药理学作用的机制之一。
OBJECTIVE: To investigate the mechanism of agmatine on the voltage-gated ion channels of hippocampal neurons in rats. Methods: The effects of agmatine on the voltage-gated sodium, potassium and calcium channels in hippocampal neurons of cultured neonatal rat hippocampus were observed by patch clamp whole-cell recording technique. Results: Agmatine (500 μmol / L) had no significant effect on sodium and potassium channels (I_A and I_K). Agmatine inhibited calcium current and its inhibitory effect increased with increasing concentration. The inhibitory rates of voltage-gated calcium currents were (21 ± 4)%, (35 ± 6)% and (35 ± 6)% at the agmatine concentrations of 0.1,0.5,1.5,10.0,50.0 and 100 μmol / 49 ± 6%, 67 ± 4%, 69 ± 6%, 86 ± 8% and 87 ± 9% respectively. The IC 50 was 1.2 ± 0.4 μmol / L. Two-way ANOVA showed that there was a significant interaction between different clamping voltage levels of the cell membrane and the inhibitory effect of agmatine on calcium current at different concentrations. CONCLUSION: Agmatine reversibly inhibits the voltage-gated calcium channel in hippocampal neurons in a concentration-dependent and voltage-dependent manner, and the blockade of calcium channel may be the mechanism of agmatine’s physiological and pharmacological effects one.