Regulation of Ca²⁺/calmodulin-dependent protein kinase II signaling within hippocampal glutamatergic postsynapses during flurazepam withdrawal.
Regulation of Ca²⁺/calmodulin-dependent protein kinase II signaling within hippocampal glutamatergic postsynapses during flurazepam withdrawal.
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DOI：
10.1155/2012/405926
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发表时间：
2012
影响因子：
3.1
通讯作者：
Tietz EI
中科院分区：
文献类型：
--
作者：
Earl DE;Das P;Gunning WT 3rd;Tietz EI
大鼠停止口服苯二氮卓类氟拉西泮（FZP）一周后，停药1天后出现戒断焦虑。FZP戒断与CA1神经元近端辐射层中含有glua1的同源α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体（AMPARs）的突触结合有关。停药2天后，Ca2+/钙调素依赖性蛋白激酶II （CaMKII）磷酸化GluA1的Ser831亚基，增加通道电导。继AMPAR增强后，含有glun2b的n -甲基- d -天冬氨酸受体（NMDARs），已知CaMKII的结合伙伴，被选择性地从突触后密度（PSD）中去除。虽然已知突触CaMKII的激活涉及到PSD的易位，但与NMDARs结合的CaMKII可能会从PSD中移除。为了区分这些可能性，目前的研究使用包埋后免疫金电镜研究停药2天后CA1辐射层突触CaMKII信号的变化。这些研究显示，CA1 psd中总CaMKIIα表达减少，但不存在自磷酸化（Thr286）表达。在药物戒断期间，从PSD中去除CaMKII-GluN2B复合物可能是一种限制ampar介导的CA1神经元高兴奋性和苯二氮卓戒断焦虑的稳态机制。
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.
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CAMKII将Ca2+通道的camkii tethers建立，建立了Ca2+信号的本地和专用集成商进行便利。
影响因子：
7.8
作者：
Hudmon, A;Schulman, H;Kim, J;Maltez, JM;Tsien, RW;Pitt, GS
通讯作者：
Pitt, GS
影响因子：
5.3
作者：
Dosemeci, A;Reese, TS;Cheng, JHT
通讯作者：
Cheng, JHT
影响因子：
56.9
作者：
Hayashi, Y;Shi, SH;Malinow, R
通讯作者：
Malinow, R
影响因子：
64.8
作者：
Bayer, KU;De Koninck, P;Schulman, H
通讯作者：
Schulman, H
DOI：
10.1073/pnas.96.6.3269
发表时间：
1999-03-16
影响因子：
11.1
作者：
Derkach, V;Barria, A;Soderling, TR
通讯作者：
Soderling, TR