Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal
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 (AMP...
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| Language: | English |
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Wiley
2012-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2012/405926 |
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| author | Damien E. Earl Paromita Das William T. Gunning Elizabeth I. Tietz |
| author_facet | Damien E. Earl Paromita Das William T. Gunning Elizabeth I. Tietz |
| author_sort | Damien E. Earl |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c7ef4dd796c74bc3a3fa155849590dc8 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Neural Plasticity |
| spelling | doaj-art-c7ef4dd796c74bc3a3fa155849590dc82025-08-20T03:24:11ZengWileyNeural Plasticity2090-59041687-54432012-01-01201210.1155/2012/405926405926Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam WithdrawalDamien E. Earl0Paromita Das1William T. Gunning2Elizabeth I. Tietz3Department of Physiology and Pharmacology, The University of Toledo College of Medicine, Health Science Campus, 3000 Arlington Avenue, Mailstop 1008, Toledo, OH 43614, USADepartment of Physiology and Pharmacology, The University of Toledo College of Medicine, Health Science Campus, 3000 Arlington Avenue, Mailstop 1008, Toledo, OH 43614, USADepartment of Pathology, The University of Toledo College of Medicine, Health Science Campus, Toledo, OH 43614, USADepartment of Physiology and Pharmacology, The University of Toledo College of Medicine, Health Science Campus, 3000 Arlington Avenue, Mailstop 1008, Toledo, OH 43614, USACessation 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.http://dx.doi.org/10.1155/2012/405926 |
| spellingShingle | Damien E. Earl Paromita Das William T. Gunning Elizabeth I. Tietz Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal Neural Plasticity |
| title | Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal |
| title_full | Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal |
| title_fullStr | Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal |
| title_full_unstemmed | Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal |
| title_short | Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II Signaling within Hippocampal Glutamatergic Postsynapses during Flurazepam Withdrawal |
| title_sort | regulation of ca2 calmodulin dependent protein kinase ii signaling within hippocampal glutamatergic postsynapses during flurazepam withdrawal |
| url | http://dx.doi.org/10.1155/2012/405926 |
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