Alterations of the GluR-B AMPA receptor subunit flip/flop expression in kainate-induced epilepsy and ischemia.
In the hippocampus, glutamatergic pathways are altered following seizure activity or transient global ischemia, both pathological conditions leading to selective neuronal degeneration. Glutamatergic receptors, and notably alpha-amino-3-hydroxy-5-methyl-4-isoxazolopropionate (AMPA) receptors, a family of glutamate receptors involved in fast synaptic transmission and in the maintenance of synaptic potentiation may play an important role in the pathological outcome. AMPA receptors are assembled from GluR-A, GluR-B, GluR-C and GluR-D polypeptides which exist in flop and flip variants, the latter allowing larger glutamate responses. Using in situ hybridization techniques, we show that kainate-induced epilepsy provokes a rapid but transient increase (50%) of GluR-B flip mRNA levels in all subregions of the hippocampus (CA1, CA3, dentate gyrus). This early phase is followed by a second, persistent GluR-B flip increase in regions in which neurons are known to be seizure-resistant (i.e. CA1 an dentate gyrus) while a 35% decrease is observed in the vulnerable CA3 area. Following global ischemia, the levels of GluR-B flip and flop variants are dramatically reduced (90-100%), well before any morphological signs of cell death, in the subiculum and CA1, two areas known to be particularly sensitive to ischemic insult. In keeping with the properties of GluR flip variants, it is suggested that altered subunit stoichiometry may lead to long-lasting enhanced efficiency of fast synaptic transmission in the epileptic hippocampus. Since GluR-B containing receptors are Ca2+ impermeable, our results also suggest altered Ca2+ permeability in the vulnerable pyramidal neurons of areas CA3 and CA1 in the epileptic and ischemic hippocampi, respectively.
Pollard
H
H
INSERM Unité 29, Paris, France.
Héron
A
A
Moreau
J
J
Ben-Ari
Y
Y
Khrestchatisky
M
M
D000818:Animals; D001483:Base Sequence; D002545:Brain Ischemia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D007608:Kainic Acid; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
D015345:Oligonucleotide Probes; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D007608:Kainic Acid