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Recent studies have shown that dysfunctions in learning and memory induced by Meth may partially reveal the mechanisms of neuronal channelopathies. Kv2.1, the primary delayed rectifying potassium channel in neurons, is responsible for mediating apoptotic current surge. However, whether Kv2.1 is involved in Meth\u2010mediated neural injury remains unknown. In the present study, the treatment of primary cultured hippocampal neurons with Meth indicated that Meth induced a time\u2010 and dose\u2010dependent augmentation of Kv2.1 protein expression, accompanied by elevated cleaved\u2010caspase 3 and declined bcl\u20102\/bax ratio. The blockage of Kv2.1 with the inhibitor GxTx\u20101E or the knockdown of the channel noticeably abrogated the pro\u2010apoptotic effects mediated by Meth, demonstrating the specific roles of Kv2.1 in Meth\u2010mediated neural damage. Additionally, the p38 mitogen\u2010activated protein kinase (MAPK) signaling was demonstrated to be involved in Meth\u2010mediated Kv2.1 upregulation and in the subsequent pro\u2010apoptotic effects, as treatment with a p38 MAPK inhibitor significantly attenuated Meth\u2010mediated Kv2.1 upregulation and cell apoptosis. Of note, PRE\u2010084, a sigma\u20101 receptor agonist, obviously attenuated Meth\u2010induced upregulation of Kv2.1 expression, neural apoptosis and p38 MAPK activation. Taken together, these results reveal a novel mechanism involved in Meth\u2010induced neural death with implications for therapeutic interventions for Meth users.<\/jats:p>","DOI":"10.1002\/jat.3576","type":"journal-article","created":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T05:21:12Z","timestamp":1514956872000},"page":"696-704","source":"Crossref","is-referenced-by-count":21,"title":["Involvement of the delayed rectifier outward potassium channel Kv2.1 in methamphetamine\u2010induced neuronal apoptosis via the p38 mitogen\u2010activated protein kinase signaling pathway"],"prefix":"10.1002","volume":"38","author":[{"given":"Jingying","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Lab of Modern Toxicology (NJMU), Ministry of Education; Department of Toxicology, School of Public Health Nanjing Medical University  818 Tianyuan East Road Nanjing Jiangsu 211166 China"},{"name":"Wuxi Center for Disease Control and Prevention  499 Jincheng Road, Liangxi District Wuxi 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