SIGNIFICANT ELECTROPHYSIOLOGICAL ALTERATIONS IN DENTATE GYRUS GLIA BUT NOT IN CA1 GLIA FROM EPILEPTIC HUMANS WITH TEMPORAL LOBE SCLEROSIS
Abstract number :
3.046
Submission category :
Year :
2002
Submission ID :
3568
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Angelique Bordey, Dennis D. Spencer. Department of Neurosurgery, Yale University School of Medicine, New Haven, CT; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT
RATIONALE: Glia have been implicated in regulating extracellular ions, in particular K+ via gap junction coupling and inwardly rectifying K+ channels. It has been speculated that epilepsy is associated with a defect in the ability of glia to properly buffer extracellular ionic changes. However, little is known about the biophysical properties of glia in sclerotic human hippocampi.
METHODS: Human glia were studied using whole-cell patch-clamp recordings in acute hippocampal slices from surgical patients with intractable temporal lobe epilepsy (TLE). Data were obtained from 12 cases: 4 cases of intractable temporal lobe epilepsy (TLE) with hippocampal sclerosis (named mesio temporal sclerosis MTS) and 8 [dsquote]control[dsquote] cases composed of 2 TLE cases without neuronal loss and 6 cases of tumors associated with seizures. Glia cells were identified based on their characteristically hyperpolarized resting membrane potential, and the lack of spontaneous action potentials and synaptic currents.
RESULTS: It was first apparent that in [dsquote]control[dsquote] tissue CA1 and dentate gyrus (DG) glia have distinct electrophysiological characteristics. CA1 glia display prominent cell-to-cell dye coupling and therefore have significantly lower membrane resistances than DG glia (see table below) that are not dye coupled. This result could indicate differences in glial K+ buffering in these two regions. In MTS patients, there is a significant decrease in inward K+ current amplitudes in DG glia compared to control tissue while no significant changes were observed in CA1 glia. These currents are carried by inwardly rectifying K+ channels. There is also a significant increase in voltage-dependent Na+ conductances in MTS glia in the dentate gyrus as compared to [dsquote]control[dsquote] tissue while CA1 glia do not express detectable Na+ conductances. The functional role of such an increase Na+ conductances is still unknown.
CONCLUSIONS: Overall, these data strongly suggest that K+ buffering by glia is impaired in the dentate gyrus but not in the CA1 region. This could lead to significant hyperexcitability originating or being amplified in this region.[table1]
[Supported by: NIH P01-NS39092-03]