Liu Shuai, Chen Rongqing
Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 Jul 30;40(7):972-980. doi: 10.12122/j.issn.1673-4254.2020.07.09.
To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition.
We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K concentration or the application of an antagonist of GABA 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.
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.
ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.
研究酸敏感离子通道（ASICs）在细胞外酸中毒条件下对小鼠海马锥体神经元电生理癫痫活动的影响。
在小鼠海马脑片灌流液中进行场电位记录时，我们研究了细胞外酸中毒对细胞外钾离子浓度升高或应用γ-氨基丁酸（GABA）受体拮抗剂诱导的癫痫活动的影响。我们还在场电位记录下测试了细胞外酸中毒对神经元兴奋性的影响，并使用ASICs特异性抑制剂评估了药理学抑制ASICs后神经元癫痫活动的变化。
在高细胞外钾离子浓度和去抑制模型中，细胞外酸中毒通过将发作样癫痫活动转变为非发作样癫痫活动，显著抑制了海马神经元的癫痫活动，并且还抑制了神经元的内在兴奋性。ASICs抑制剂并未拮抗细胞外酸中毒对发作性癫痫活动和神经元内在兴奋性的抑制作用，但在高细胞外钾离子浓度和去抑制模型中，均加剧了细胞外酸中毒条件下神经元的非发作性癫痫活动。
ASICs可通过直接作用于兴奋性神经元，差异性地调节发作样和非发作样癫痫活动。
