细胞外钙离子浓度对海马神经元兴奋性的影响(英文)

目的在不同的生理、病理情况下,中枢神经系统细胞外钙离子浓度([Ca2 ]o)下降,导致神经元兴奋性增高。本研究的主要目的是探讨低钙条件下神经元兴奋性增高的机制,从而为临床治疗神经元过度兴奋性疾病探索新的治疗途径。方法应用穿孔膜片钳及细胞培养技术,记录不同细胞外钙离子浓度对海马神经元兴奋性的影响。结果低钙环境使神经元兴奋性显著增高,阈电位水平显著降低,动作电位幅度显著增高。并且出乎意料的是,mAHP拮抗剂apamin及sAHP拮抗剂Iso对海马神经元兴奋性的影响没有统计学的意义。作为INaP拮抗剂,低浓度的河豚毒(TTX)虽然阻断了低钙环境中神经元兴奋性的增加,但同时也阻断了正常钙离子浓度下的动作电位的发放。结论低钙环境中海马神经元阈电位的显著下降可能是导致神经元兴奋性增高的主要原因。

Mechanisms underlying low [Ca~(2 )]_o-induced increased excitability of hippocampal neurons

Objective Concentration of extracellular calcium ([Ca2 ]o) in the central nervous system decreases substantially in different conditions. It results in facilitating neuronal excitability. The goal of this study is to examine the mechanisms of enhanced neuronal excitation in low [Ca2 ]o in order to provide new clues to treat the hyperexcitability diseases in clinic. Methods Whole-cell patch-clamp technique and neuron culture were used in the study. Results The firing threshold of cultured hippocampal neurons decreased markedly in low [Ca2 ]o saline. Unexpectedly, apamine and isoprenaline, antagonists of medium afterhyperpolarization (mAHP) and slowAHP(sAHP) respectively, had no statistic significant effect on excitability of neurons. TTX at a low concentration was sufficient to inhibit INaP, which blocked the increase of firing frequency in low [Ca2 ]o. It also reduced the number of spikes in normal [Ca2 ]o. Conclusion These results suggest that in cultured hippocampal neurons, modulation of spiking threshold but notAHP may cause the increased excitability in low [Ca2 ]o.