南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (07): 972-980.doi: 10.12122/j.issn.1673-4254.2020.07.09

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酸敏感离子通道对细胞外酸化时海马锥体神经元发作性和非发 作性癫痫样活动具有不同调控作用

刘 帅，陈荣清   

  • 出版日期:2020-07-20 发布日期:2020-07-20
  • 基金资助:

Acid-sensing ion channels differentially affect ictal-like and non-ictal-like epileptic activities of mouse hippocampal pyramidal neurons in acidotic extracellular pH

  

  • Online:2020-07-20 Published:2020-07-20

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摘要： 目的 探讨细胞外酸化时酸敏感离子通道（ASICs）对癫痫样活动的调控作用及其潜在机制。方法 在海马脑片上使用场电位记录方法研究细胞外酸化对高钾环境的高钾模型和使用GABAA受体拮抗剂的去抑制模型的癫痫样活动的影响；使用全细 胞膜片钳技术记录方法研究细胞外酸化对神经元的兴奋性的影响；使用ASICs拮抗剂研究ASICs对癫痫样活动和神经元兴奋性影响。结果 细胞外酸化在高钾模型明显减弱癫痫样放电的程度（P<0.001），明显减少癫痫样活动的单次峰电位数量（P<0.01）及其幅度（P<0.001），并且癫痫样放电的模式从发作性癫痫样放电转换为发非发作性癫痫样放电；ASICs的拮抗剂不能阻断细胞外酸化对神经元兴奋性的抑制作用以及对癫痫样放电的模式的转换的作用；ASICs的拮抗剂在细胞外酸化条件下可增强非发作性癫痫样放电的活动（P<0.05）。在去抑制模型中，细胞外酸化对癫痫样活动的抑制和癫痫放电模式的转换作用与高钾模型一致；细胞外酸化可明显升高动作电位的阈电位（P<0.01）、半波宽（P<0.05）和达到动作电位峰值的时间（P<0.01），可明显降低神经元兴奋性，并且这种减弱作用不能被ASICs拮抗剂和GABAA受体拮抗剂阻断。结论 ASICs可以直接作用于兴奋性神经元，对癫痫样放电中的发作性癫痫样放电和非发作性癫痫样放电的活动有不同的调控作用。

关键词: 癫痫, 细胞外酸化, 酸敏感离子通道, ASICs, 场电位记录

Abstract: Objective To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition. Methods We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K + concentration or the application of an antagonist of GABAA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs. Results Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K + ]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K+]o and disinhibition models. Conclusion ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.

Key words: epilepsy, extracellular acidosis, acid-sensitive ion channels, ASICs, field potential recording