Broberg Marita, Pope Kenneth J, Nilsson Michael, Wallace Angus, Wilson Jodie, Willoughby John O
Center for Neuroscience and Department of Medicine, Flinders University, Adelaide, South Australia, Australia.
J Neurosci Res. 2007 Mar;85(4):906-18. doi: 10.1002/jnr.21162.
Extracellular ion concentrations change during seizures in seizure models. K(+) increases and Ca(2+) decreases, resulting from population discharges, enhanced neuronal excitability, though not obviously before seizure onset. In acute pharmacological epilepsy models, there are striking increases in preictal high-frequency (gamma) electroencephalographic (EEG) activity. It is not known whether enhanced gamma EEG results in ionic changes, because gamma and ions have not been measured simultaneously. In this study, unanesthetized, paralyzed rats were given intravenous injections of kainic acid or picrotoxin to induce EEG discharges. Changes in EEG, K(+), and Ca(2+) in cortex and hippocampus were recorded. Kainic acid caused small K(+) fluctuations, without a temporal relationship of these with increased gamma EEG or with onset of discharges. Gamma EEG increases after picrotoxin also failed to affect K(+) and Ca(2+). Picrotoxin-induced electrical discharges led to K(+) rises of >9 mM and Ca(2+) falls of 0.1-0.2 mM. Kainic acid-induced discharges generated only moderate (2-3 mM) rises in K(+) and no changes in Ca(2+). In both models, there were large potassium rises (15-80 mM) and calcium falls (>0.5 mM), suggesting spreading depressions. Small K(+) fluctuations after kainic acid are consistent with disruption in potassium homeostasis, possibly because of depolarization of astrocytes. To reveal possible latent K(+) or Ca(2+) changes, we injected fluorocitrate intracortically to impair astrocytic function, before administering picrotoxin. Even fluorocitrate did not cause gamma-related ion changes but did cause low-magnitude, transient, potassium increases and slower potassium homeostasis during discharges, minor changes consistent with involvement of both astrocytes and neurons in K(+) regulation. (c) 2007 Wiley-Liss, Inc.
在癫痫模型中，癫痫发作期间细胞外离子浓度会发生变化。由于群体放电和神经元兴奋性增强，细胞外钾离子浓度升高，细胞外钙离子浓度降低，不过在癫痫发作开始前这种变化并不明显。在急性药理学癫痫模型中，发作前高频（γ）脑电图（EEG）活动会显著增加。目前尚不清楚增强的γ脑电图是否会导致离子变化，因为尚未同时测量γ和离子。在本研究中，对未麻醉、麻痹的大鼠静脉注射 kainic 酸或印防己毒素以诱导 EEG 放电。记录了皮层和海马中 EEG、细胞外钾离子浓度和细胞外钙离子浓度的变化。Kainic 酸引起细胞外钾离子浓度的小幅波动，这些波动与增强的γ脑电图或放电开始之间没有时间关系。印防己毒素引起的γ脑电图增加也未能影响细胞外钾离子浓度和细胞外钙离子浓度。印防己毒素诱导的放电导致细胞外钾离子浓度升高超过 9 mM，细胞外钙离子浓度下降 0.1 - 0.2 mM。Kainic 酸诱导的放电仅使细胞外钾离子浓度适度升高（2 - 3 mM），而细胞外钙离子浓度没有变化。在这两种模型中，都有大量的钾离子升高（15 - 80 mM）和钙离子下降（>0.5 mM），提示存在扩散性抑制。Kainic 酸后细胞外钾离子浓度的小幅波动与钾离子稳态的破坏一致，可能是由于星形胶质细胞的去极化。为了揭示可能潜在的细胞外钾离子浓度或细胞外钙离子浓度变化，在给予印防己毒素之前，我们向皮层内注射氟柠檬酸以损害星形胶质细胞功能。即使氟柠檬酸也未引起与γ相关的离子变化，但确实导致了低幅度、短暂的钾离子增加以及放电期间钾离子稳态减慢，这些微小变化与星形胶质细胞和神经元参与细胞外钾离子浓度调节一致。（c）2007 Wiley - Liss，Inc.
