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Regulation of Ca2+Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal
Joint Authors
Earl, Damien E.
Das, Paromita
Gunning, William T.
Tietz, Elizabeth I.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-07-05
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Cessation of one-week oral administration of the benzodiazepine flurazepam (FZP) to rats results in withdrawal anxiety after 1 day of withdrawal.
FZP withdrawal is correlated with synaptic incorporation of homomeric GluA1-containing α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) in the proximal stratum radiatum of CA1 neurons.
After 2 days of withdrawal, Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylates GluA1 subunits at Ser831, increasing channel conductance.
Secondary to AMPAR potentiation, GluN2B-containing N-methyl-D-aspartate receptors (NMDARs), known binding partners of CaMKII, are selectively removed from the postsynaptic density (PSD).
While activation of synaptic CaMKII is known to involve translocation to the PSD, CaMKII bound to NMDARs may be removed from the PSD.
To distinguish these possibilities, the current studies used postembedding immunogold electron microscopy to investigate alterations in CaMKII signaling at CA1 stratum radiatum synapses after 2 days of FZP withdrawal.
These studies revealed decreased total, but not autophosphorylated (Thr286) CaMKIIα expression in CA1 PSDs.
The removal of CaMKII-GluN2B complexes from the PSD during drug withdrawal may serve as a homeostatic mechanism to limit AMPAR-mediated CA1 neuron hyperexcitability and benzodiazepine withdrawal anxiety.
American Psychological Association (APA)
Earl, Damien E.& Das, Paromita& Gunning, William T.& Tietz, Elizabeth I.. 2012. Regulation of Ca2+Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal. Neural Plasticity،Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-1002410
Modern Language Association (MLA)
Earl, Damien E.…[et al.]. Regulation of Ca2+Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal. Neural Plasticity No. 2012 (2012), pp.1-12.
https://search.emarefa.net/detail/BIM-1002410
American Medical Association (AMA)
Earl, Damien E.& Das, Paromita& Gunning, William T.& Tietz, Elizabeth I.. Regulation of Ca2+Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal. Neural Plasticity. 2012. Vol. 2012, no. 2012, pp.1-12.
https://search.emarefa.net/detail/BIM-1002410
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1002410