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Keywords:

  • ions;
  • homeostasis;
  • seizure;
  • astrocytes

Abstract

Extracellular ion concentrations change during seizures in seizure models. [K+]o increases and [Ca2+]o 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+]o, and [Ca2+]o in cortex and hippocampus were recorded. Kainic acid caused small [K+]o 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+]o and [Ca2+]o. Picrotoxin-induced electrical discharges led to [K+]o rises of >9 mM and [Ca2+]o falls of 0.1–0.2 mM. Kainic acid-induced discharges generated only moderate (2–3 mM) rises in [K+]o and no changes in [Ca2+]o. In both models, there were large potassium rises (15–80 mM) and calcium falls (>0.5 mM), suggesting spreading depressions. Small [K+]o fluctuations after kainic acid are consistent with disruption in potassium homeostasis, possibly because of depolarization of astrocytes. To reveal possible latent [K+]o or [Ca2+]o 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+]o regulation. © 2007 Wiley-Liss, Inc.