Inhibitory gene expression of the Cav3.1 T-type calcium channel to improve neuronal injury induced by lidocaine hydrochloride

• Published in: European journal of pharmacology Vol. 775; pp. 43 - 49
• Main Authors: Wen, Xianjie, Xu, Shiyuan, Zhang, Qingguo, Li, Xiaohong, Liang, Hua, Yang, Chenxiang, Wang, Hanbing, Liu, Hongzhen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2016
• Subjects: Anesthetics, Local - adverse effects; Anesthetics, Local - pharmacology; Apoptosis; Calcium Channels, T-Type - genetics; Calcium Channels, T-Type - metabolism; Cav3.1; Cell Line, Tumor; Cell Survival; Gene Expression Regulation, Neoplastic; Humans; Lidocaine - adverse effects; Lidocaine - pharmacology; Lidocaine hydrochloride; Neurons - drug effects; Neurons - pathology; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; SH-SY5Y cells; 2-(4-Amidinophenyl)−6-indolecarbamidine dihydrochloride (PubChem CID: 160166; Lidocaine hydrochloride; Propidium iodide (PubChem CID: 104981); SH-SY5Y cells; Calcium ion (PubChem CID: 271); Cav3.1; Lidocaine hydrochloride (PubChem CID: 6314); p38 MAPK
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2016.02.019

Cav3.1 is a low-voltage-activated (LVA) calcium channel that plays a key role in regulating intracellular calcium ion levels. In this study, we observed the effects of lidocaine hydrochloride on the pshRNA-CACNA1G-SH-SY5Y cells that silenced Cav3.1 mRNA by RNA interference, and investigated the roles of p38 MAPK in these effects. We constructed the pNC-puro-CACNA1G-SH-SY5Y cells and pshRNA-CACNA1G –SH-SY5Y cells by the RNA interference. All the cells were cultured with or without 10mM lidocaine hydrochloride for 24h. The cell morphology, cell viability, Cav3.1 and p38 protein expression, cell apoptosis rate and intracellular calcium ion concentration were detected. We found that all cells treated with 10mM lidocaine hydrochloride for 24h showed cellular rounding, axonal regression, and cellular floating. Compared with the cells in SH-SY5Y+Lido group and NC+Lido group, those in the RNAi+Lido group showed similar changes, but of smaller magnitude. Additionally, following lidocaine hydrochloride all cells displayed increased Cav3.1 and p38 MAPK protein, apoptosis rate, and intracellular calcium ion levels; however,these changes in the RNAi+Lido group were less pronounced than in the SH-SY5Y+Lido and NC+Lido groups. The cell viability decreased following lidocaine hydrochloride treatment, but viability of the cells in the RNAi+Lido group was higher than in the SH-SY5Y+Lido and NC+Lido groups. The results showed that Cav3.1 may be involved in neuronal injury induced by lidocaine hydrochloride and that p38 MAPK phosphorylation was reduced upon Cav3.1 gene silencing.