Premium
Changes in Flip/Flop Splicing of Astroglial AMPA Receptors in Human Temporal Lobe Epilepsy
Author(s) -
Seifert Gerald,
Schröder Wolfgang,
Hinterkeuser Stefan,
Schumacher Thekla,
Schramm Johannes,
Steinhäuser Christian
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.10.x
Subject(s) - ampa receptor , hippocampal sclerosis , kainate receptor , epilepsy , neuroscience , glutamate receptor , hippocampal formation , epileptogenesis , biology , cx3cr1 , temporal lobe , long term potentiation , receptor , chemokine receptor , biochemistry , chemokine
Summary: Purpose: Recent data suggested a role for glial cells in epilepsy. This study sought to identify and functionally characterize AMPA receptors expressed by astrocytes in human hippocampal tissue resected from patients with intractable temporal lobe epilepsy. Methods: Patch‐clamp and fast application methods were combined to investigate astrocytes in situ and after fresh isolation from the stratum radiatum of the hippocampal CA1 subfield. Relying on presurgical and histopathologic analysis, we divided human specimens into two groups, Ammon's horn sclerosis (AHS) and lesion‐associated epilepsy. Results: Fast application of glutamate and kainate evoked receptor currents in all cells studied. Reversal‐potential analysis revealed an intermediate Ca 2+ permeability of the receptor channels that did not vary between the two groups of patients. However, preapplication of the AMPA receptor–specific modulator, cyclothiazide, disclosed differences in flip‐flop splicing. This treatment considerably enhanced the receptor conductance, with potentiation being significantly stronger in cells from AHS specimens compared with lesion‐associated cells, suggesting upregulation of AMPA receptor flip splice variants in astrocytes of the sclerotic tissue. Conclusions: Compelling evidence has been accumulated showing direct and rapid signaling between neurons and glial cells. Our data suggest that in AHS patients, neuronally released glutamate will lead to an enhanced and prolonged depolarization of astrocytes, which might be involved in seizure generation and spread in this particular condition of human temporal lobe epilepsy.