期刊
JOURNAL OF NEUROCHEMISTRY
卷 121, 期 4, 页码 662-671出版社
WILEY
DOI: 10.1111/j.1471-4159.2012.07717.x
关键词
anterior cingulate cortex; NMDA receptor; NR2B subunit; phosphorylated CaMKII; post-synaptic binding; visceral hypersensitivity
资金
- Research Grant Council of the Hong Kong Special Administrative Region, China, RGC [160810, 160811]
- National Natural Science Foundation of China [30800512, 9680020]
- City University of Hong Kong [9380053]
- City University Neuroscience research infrastructure [9610211]
The NR2B subunit of NMDA receptor in the anterior cingulate cortex (ACC) is up-regulated in viscerally hypersensitive (VH) rats induced by colonic anaphylaxis. It plays a critical role in modulation of ACC sensitization and visceral pain responses. Given the key role of calcium/calmodulin-dependent protein kinase II (CaMKII) in synaptic plasticity and behavior learning and memory, we hypothesize that phosphorylation of CaMKII binding to NR2B mediates visceral pain in VH states. We performed in vivo electroporation of CaMKII siRNA produced inhibition of colorectal distension-induced visceromotor response in the VH rats. The NR2B, CaMKII and P-CaMKII-Thr286 protein levels were increased in 180%, 220% and 304% fold in the post-synaptic density (PSD) fraction in VH rats separately. Western blotting following co-immunoprecipitation showed that P-CaMKII-Thr286 bound to NR2B in the PSD, which was increased to 267% of control in VH rats. Administration of CaMKII antagonist Antennapedia-CaMKIINtide suppressed visceromotor response in VH rats in parallel with decrease of NR2B levels and reduction of the NR2B-P-CaMKII-Thr286 protein complex in PSD. In conclusion, CaMKII is a critical signaling molecule in the ACC glutamatergic synaptic transmission and phosphorylation of CaMKII at Thr286, which binds to NR2B subunit at post-synaptic site, modulates visceral pain in viscerally hypersensitive state.
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