Changes in flip/flop splicing of astroglial AMPA receptors in human temporal lobe epilepsy.
OBJECTIVE
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 Ca2+ 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.
Experimental Neurobiology, Dept of Neurosurgery, University of Bonn, Sigmund-Freud-Strasse 25, 53125 Bonn, Germany.
Gerald
G
Seifert
Wolfgang
W
Schröder
Stefan
S
Hinterkeuser
Thekla
T
Schumacher
Johannes
J
Schramm
Christian
C
Steinhäuser
D001253:Astrocytes / Q000378:metabolism*; D001927:Brain Diseases / Q000150:complications; D002118:Calcium / Q000378:metabolism; D004274:DNA, Recombinant; D004553:Electric Conductivity; D004833:Epilepsy, Temporal Lobe / Q000209:etiology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D014644:Genetic Variation; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D009457:Neuroglia / Q000502:physiology; D010539:Permeability; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D012598:Sclerosis; D013702:Temporal Lobe
D004274:DNA, Recombinant; D018091:Receptors, AMPA; D002118:Calcium