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细胞内钙缓冲剂Bapta对海马神经元癫痫样活动的影响

The Effect of Intracellular Calcium Buffer Bapta on Epileptiform Activity of Hippocampal Neurons.

作者信息

Zinchenko V P, Teplov I Yu, Tyurin F V, Malibayeva A E, Kairat B K, Tuleukhanov S T

机构信息

Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino 142290, Russia.

Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan.

出版信息

Int J Mol Sci. 2025 Aug 6;26(15):7596. doi: 10.3390/ijms26157596.

DOI:10.3390/ijms26157596
PMID:40806722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347522/
Abstract

The rhythm of epileptiform activity occurs in various brain injuries (ischemia, stroke, concussion, mechanical damage, AD, PD). The epileptiform rhythm is accompanied by periodic Ca pulses, which are necessary for the neurotransmitter release, the repair of damaged connections between neurons, and the growth of new projections. The duration and amplitude of these pulses depend on intracellular calcium-binding proteins. The effect of the synthetic fast calcium buffer BAPTA on the epileptiform activity of neurons induced by the GABA(A)-receptor inhibitor, bicuculline, was investigated in a 14-DIV rat hippocampal culture. In the epileptiform activity mode, neurons periodically synchronously generate action potential (AP) bursts in the form of paroxysmal depolarization shift (PDS) clusters and their corresponding high-amplitude Ca pulses. Changes in the paroxysmal activity and Ca pulses were recorded continuously for 10-11 min as BAPTA accumulated. It was shown that during BAPTA accumulation, transformation of neuronal patch activity occurs. Moreover, GABAergic and glutamatergic neurons respond differently to the presence of calcium buffer. Experiments were performed on two populations of neurons: a population of GABAergic neurons that responded selectively to ATPA, a calcium-permeable GluK1 kainate receptor agonist, and a population of glutamatergic neurons with a large amplitude of cluster depolarization (greater than -20 mV). These neurons made up the majority of neurons. In the population of GABAergic neurons, during BAPTA accumulation, the amplitude of PDS clusters decreases, which leads to a switch from the PDS mode to the classical burst mode with an increase in the electrical activity of the neuron. In glutamatergic neurons, the duration of PDS clusters decreased during BAPTA accumulation. However, the amplitude changed little. The data obtained showed that endogenous calcium-binding proteins play a significant role in switching the epileptiform rhythm to the recovery rhythm and perform a neuroprotective function by reducing the duration of impulses in excitatory neurons and the amplitude of impulses in inhibitory neurons.

摘要

癫痫样活动的节律出现在各种脑损伤(缺血、中风、脑震荡、机械损伤、阿尔茨海默病、帕金森病)中。癫痫样节律伴随着周期性的钙脉冲,这对于神经递质释放、受损神经元间连接的修复以及新突起的生长是必需的。这些脉冲的持续时间和幅度取决于细胞内钙结合蛋白。在14日龄大鼠海马培养物中研究了合成的快速钙缓冲剂BAPTA对由GABA(A)受体抑制剂荷包牡丹碱诱导的神经元癫痫样活动的影响。在癫痫样活动模式下,神经元以阵发性去极化偏移(PDS)簇的形式周期性同步产生动作电位(AP)爆发及其相应的高幅度钙脉冲。随着BAPTA积累,连续记录阵发性活动和钙脉冲的变化10 - 11分钟。结果表明,在BAPTA积累过程中,神经元膜片活动发生转变。此外,GABA能神经元和谷氨酸能神经元对钙缓冲剂的存在反应不同。实验在两类神经元群体上进行:一类是对钙通透的GluK1红藻氨酸受体激动剂ATPA有选择性反应的GABA能神经元群体,另一类是簇状去极化幅度大(大于 - 20 mV)的谷氨酸能神经元群体。这些神经元构成了神经元的大多数。在GABA能神经元群体中,在BAPTA积累过程中,PDS簇的幅度减小,这导致从PDS模式转变为经典爆发模式,同时神经元的电活动增加。在谷氨酸能神经元中,BAPTA积累过程中PDS簇的持续时间缩短。然而,幅度变化不大。所获得的数据表明,内源性钙结合蛋白在将癫痫样节律转变为恢复节律中起重要作用,并通过减少兴奋性神经元中冲动的持续时间和抑制性神经元中冲动的幅度发挥神经保护功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d953/12347522/0a841bfcba18/ijms-26-07596-g006.jpg
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