Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus.
Profound astrogliosis coincident with neuronal cell loss is universally described in human and animal models of temporal lobe epilepsy (TLE). In the kainic acid-induced status epilepticus (SE) model of TLE, astrocytes in the hippocampus become reactive soon after SE and before the onset of spontaneous seizures. To determine if astrocytes in the hippocampus exhibit changes in function soon after SE, we recorded from SR101-labeled astrocytes using the whole-cell patch technique in hippocampal brain slices prepared from control and kainic-acid-treated rats. Glutamate transporter-dependent currents were found to have significantly faster decay time kinetics and in addition, dye coupling between astrocytes was substantially increased. Consistent with an increase in dye coupling in reactive astrocytes, immunoblot experiments demonstrated a significant increase in both glial fibrillary acidic protein (GFAP) and connexin 43, a major gap junction protein expressed by astrocytes. In contrast to what has been observed in resected tissue from patients with refractory epilepsy, changes in potassium currents were not observed shortly after KA-induced SE. While many changes in neuronal function have been identified during the initial period of low seizure probability in this model of TLE, the present study contributes to the growing body of literature suggesting a role for astrocytes in the process of epileptogenesis.
Takahashi
D K
DK
Interdepartmental Program in Neuroscience, University of Utah, Salt Lake City, UT 84108, USA.
Vargas
J R
JR
Wilcox
K S
KS
D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018031:Connexin 43 / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
D018031:Connexin 43; D003292:Convulsants; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D007608:Kainic Acid