Key result
In the tremor rat model hippocampus, CaV1.2 and CaM expression were significantly increased while p-CaMKII was decreased, suggesting this pathway's involvement in epileptogenesis.
Abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway and increased intracellular calcium may be involved in epileptogenesis in tremor rat models and Mg2+-free treated neurons.
Hypothesis-generating for CaV1.2/CaMKII in epileptogenesis; leaves open any human therapeutic relevance.
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.
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Lv et al. (2015) studied Epilepsy (n=30). Tremor rat model (genetic mutation) and Mg2+-free solution vs. Normal Wistar rats and normal physiological solution was evaluated on Expression levels of CaV1.2, CaM, and p-CaMKII. In the tremor rat model hippocampus, CaV1.2 and CaM expression were significantly increased while p-CaMKII was decreased, suggesting this pathway's involvement in epileptogenesis.
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