Intracellular pH modulates spontaneous and epileptiform bioelectric activity of hippocampal CA3-neurones
Intracellular pH modulates spontaneous and epileptiform bioelectric activity of hippocampal CA3-neurones
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DOI：
10.1016/s0924-977x(99)00063-2
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发表时间：
2000-03-01
影响因子：
5.6
通讯作者：
Wiemann, M
中科院分区：
文献类型：
--
作者：
Bonnet, U;Bingmann, D;Wiemann, M
越来越多的证据表明细胞内的自由质子参与皮层神经元电活动的调节。在这项研究中，我们证明了弱酸丙酸盐（2.5-20 mM）的应用瞬时降低海马切片中BCECF-AM负载的CA 3-神经元的细胞内PH（pH（i））。这种酸化的可预测性促使我们使用丙酸盐作为工具来研究pH（i）对CA 3神经元的自发生物电活动（SBA）和癫痫样活动（EA，由荷包牡丹碱、咖啡因或低镁诱导）的影响：SEA和EA被2-20 mM丙酸盐短暂抑制-与短暂的神经元酸化一致。由于Na+ /H+交换剂（NHE）的激活参与神经元酸中毒的恢复，已知单独抑制NHE可增加海马神经元细胞内游离质子的活性，因此我们检测了NHE阻断剂阿米洛利（0.5-1 mM）或HOE 642（200 μ M）对CA 3神经元SEA和EA的影响。长期应用NHE抑制剂单独连续抑制SEA和EA，恢复期间额外暴露于弱碱性三甲胺（5-10 mM）。丙酸盐和NHE-阻滞剂的同时施用加强了神经元活性的抑制。总之，这些结果表明，细胞内酸化抑制海马CA 3-神经元的生物电活动。这支持了pH（i）有助于控制皮质兴奋性的假设。(C)2000爱思唯尔科技有限公司。保留所有权利。
A growing body of evidence hints at intracellular free protons to be involved in the modulation of electric activity of cortical neurones. In this study we demonstrate that application of the weak acid propionate (2.5-20 mM) transiently lowers intracellular PH (pH(i)) of BCECF-AM loaded CA3-neurones in hippocampal slices. The predictability of this acidification prompted us to use propionate as a tool to investigate effects of pH(i) on spontaneous bioelectric activity (SBA) and epileptiform activity (EA, induced by bicuculline, caffeine or low magnesium) of CA3 neurones: SEA and EA were transiently suppressed by 2-20 mM propionate - coinciding with the transient neuronal acidification. As activation of Na+ /H+-exchangers (NHE) is involved in the recovery from neuronal acidosis and NHE-inhibition alone is known to increase the activity of intracellular free protons of hippocampal neurones, we tested the effect of the NHE-blockers amiloride (0.5-1 mM) or HOE642 (200 mu M) on SEA and EA of CA3-neurones. Long-term application of NHE-inhibitors alone continuously suppressed SEA and EA, which recovered during additional exposure to the weak base trimethylamine (5-10 mM). Simultaneous administration of propionate and NHE-blockers intensified the inhibition of neuronal activity. Together, these results indicate that intracellular acidification inhibits bioelectric activity of hippocampal CA3-neurones. This supports the hypothesis that pH(i) contributes to the control of cortical excitability. (C) 2000 Elsevier Science B.V. All rights reserved.