AMPA glutamate receptors and their flip and flop mRNAs in human hippocampus

Eastwood, Sharon L.; Burnet, Philip W.J.; Beckwith, Jason; Kerwin, Robert; Harrison, Paul J.

doi:10.1097/00001756-199406270-00007

Cited by 11 publications

(17 citation statements)

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“…These differences may be due to the longer post‐mortem delay in the specimens they studied, with consequent mRNA degradation. Our observation that there is little or no flop variant of either subunit in CA3 agrees with Eastwood et al . (1994) but differs in that they report the GluR1 flip variant as limited to CA3; whereas we observe it in all CA fields.…”

Section: Discussionsupporting

confidence: 93%

“…1994; 26 ± 11 h compared with less than 30 min post‐surgical in this study). The GluR2 flip and flop localization patterns we report and those of the Eastwood et al . (1994) study are generally in agreement, although we have observed little GluR2 flip in the dentate and none in the subiculum.…”

Section: Discussionsupporting

confidence: 80%

“…Further, they report the GluR1 flop in the dentate, all CA fields and subiculum, but we observe it mainly in the dentate. The GluR1 and GluR2 localization data of this study (Eastwood et al . 1994) is almost the reverse of our observations.…”

Section: Discussionmentioning

confidence: 61%

“…1994) is almost the reverse of our observations. The reason for such discrepancy is not clear, though post‐mortem delay may play a role (Eastwood et al . 1994; 26 ± 11 h compared with less than 30 min post‐surgical in this study).…”

Section: Discussionmentioning

confidence: 99%

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Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus

Lanerolle¹,

Eid

Campe³

et al. 1998

Eur J of Neuroscience

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The AMPA-type glutamate receptor subunits GluR1 and GluR2/3 were localized by immunohistochemistry with subunit-specific antibodies in hippocampi removed surgically from patients with temporal lobe epilepsy for the control of seizures. The flip and flop splice variants of the subunits were localized by in situ hybridization histochemistry with specific oligoprobes. In patient hippocampi that were not the seizure focus, the GluR1 subunit proteins were diffusely expressed on the dendrites of neurons in all regions. In contrast, in these same hippocampi, the GluR2/3 subunit proteins were expressed strongly on the soma and proximal dendrites of principal neurons in all regions. The flip variant of these subunits was localized in the hilus and fields of Ammon's Horn (CA), while the flop variants were prominent on the dentate granule cells. In the epileptogenic hippocampus, while immunoreactivity was decreased in all fields that showed neuronal loss, there was an increased expression of GluR1 on the dendritic excrescences on the proximal dendrites of hilar neurons and CA3 pyramidal neurons, as well as expression of GluR2/3 in hilar neuron excrescences. Electron microscopic examination confirmed that the GluR1 immunoreactivity was only in dendritic processes, particularly dense at the postsynaptic membranes. Such expression of GluR1 may provide for an enhanced glutamatergic response by these neurons. GluR2/3 was also significantly increased on the dendrites of dentate granule cells in the epileptogenic hippocampus and may provide some protection against excitotoxic injury by reducing calcium flux into neurons.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus

Lanerolle¹,

Eid

Campe³

et al. 1998

Eur J of Neuroscience

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“…These spliced forms are expressed in a cell type-specific manner, and may be developmentally regulated. For example, in both humans and rats, flop isoforms predominate over flip in the adult hippocampal CA1 region and in the dentate gyrus [Eastwood et al, 1994]. The flip-flop ratio appears to have an important role in defining the kinetic properties of AMPA receptors.…”

Section: Introductionmentioning

confidence: 99%

Role of excitatory amino acids in developmental epilepsies

Raol

Lynch

Brooks‐Kayal

2001

Ment. Retard. Dev. Disabil. Res. Rev.

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Altered excitatory amino acid (EAA) neurotransmission, mediated primarily by glutamate, is a major cause of the imbalance of excitation and inhibition which characterizes both early development and epileptogenesis. Glutamate's actions are mediated by three classes of receptors: NMDA, non-NMDA (AMPA and kainate), and metabotropic. Several features of normal EAA development contribute to hyperexcitability in the immature brain, making it more prone to development of seizures. These features include increased density of NMDA receptors, differences in NMDA receptor subunit composition and activation kinetics, which result in reduced voltage-dependent Mg(2+) blockade and longer receptor openings in early development. Also, the unique subunit composition of AMPA receptors present at synapses during early development results in increased Ca(2+) influx. These and other differences in EAA signaling, in combination with developmental alterations in inhibitory neurotransmission, contribute to the increased seizure susceptibility seen in young animals and children. In turn, seizures themselves may alter EAA neurotransmission in an age-dependent manner. Age related changes in excitatory neurotransmission may, therefore, lead to differences in basic mechanisms of epileptogenesis between the immature and mature brain, and may also alter the activity and efficacy of antiepileptic drugs in the pediatric age group.

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ASF/SF2 and SC35 regulate the glutamate receptor subunit 2 alternative flip/flop splicing

Crovato¹,

Egebjerg²

2005

FEBS Letters

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The properties of the glutamate receptor subunits 1-4 (GluR1-4) are influenced by the alternative splicing of two homologous and mutually exclusive exons flip and flop. The flip form is most abundant during early development, while the flop form is dominant in adults. From transfections with a GluR2 mini-gene we show that flip is the preferred splice form in all tested cell lines, but coexpression of the SR-proteins ASF/SF2 and SC35 increases the flop to flip splice ratio. The increased flop incorporation depends on ASF/SF2-and SC35-dependent enhancer elements located in the flop exon, which stimulate the splicing between the flop exon and the preceding exon 13.

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AMPA glutamate receptors and their flip and flop mRNAs in human hippocampus

Cited by 11 publications

References 0 publications

Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus

Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus

Role of excitatory amino acids in developmental epilepsies

ASF/SF2 and SC35 regulate the glutamate receptor subunit 2 alternative flip/flop splicing

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