title: Abnormal alterations in the Ca²⁺/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg²⁺-free solution.
abstract: Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence‑like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+‑free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p‑CaMKII; Thr‑286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p‑CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p‑CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co‑localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+‑free solution.
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Xintong
authors: X
authors: Lv
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Feng
authors: F
authors: Guo
authors: Department of Neurology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Xiaoxue
authors: X
authors: Xu
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Zaixing
authors: Z
authors: Chen
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Xuefei
authors: X
authors: Sun
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Dongyu
authors: D
authors: Min
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Yonggang
authors: Y
authors: Cao
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Xianbao
authors: X
authors: Shi
authors: Molecular Therapeutics Research Group, School of Pharmacy, Queen's University, Belfast BT7 1NN, United Kingdom.
authors: Lei
authors: L
authors: Wang
authors: Molecular Therapeutics Research Group, School of Pharmacy, Queen's University, Belfast BT7 1NN, United Kingdom.
authors: Tianbao
authors: T
authors: Chen
authors: Molecular Therapeutics Research Group, School of Pharmacy, Queen's University, Belfast BT7 1NN, United Kingdom.
authors: Chris
authors: C
authors: Shaw
authors: College of Life and Health Sciences, Northeastern University, Shenyang, Liaoning 110001, P.R. China.
authors: Huiling
authors: H
authors: Gao
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Liying
authors: L
authors: Hao
authors: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China.
authors: Jiqun
authors: J
authors: Cai
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D002478:Cells, Cultured; D004569:Electroencephalography; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D008274:Magnesium / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014202:Tremor / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D020746:Calcium Channels, L-Type; D002147:Calmodulin; C419385:L-type calcium channel alpha(1C); D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D008274:Magnesium; D002118:Calcium