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: Xintong Lv, Feng Guo, Xiaoxue Xu, Zaixing Chen, Xuefei Sun, Dongyu Min, Yonggang Cao, Xianbao Shi, Lei Wang, Tianbao Chen, Chris Shaw, Huiling Gao, Liying Hao, Jiqun Cai
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 5 Pg. 6663-71 (Nov 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 26299765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channels, L-Type
• Calmodulin
• L-type calcium channel alpha(1C)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Magnesium
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Calcium Channels, L-Type (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Calmodulin (metabolism)
• Cells, Cultured
• Electroencephalography
• Hippocampus (cytology, metabolism, physiopathology)
• Magnesium (metabolism)
• Neurons (cytology, metabolism, pathology)
• Rats
• Rats, Wistar
• Signal Transduction
• Tremor (metabolism, physiopathology)