title: Effect of methamphetamine on the microglial damage: role of potassium channel Kv1.3.
abstract: Methamphetamine (Meth) abusing represents a major public health problem worldwide. Meth has long been known to induce neurotoxicity. However, the mechanism is still remained poorly understood. Growing evidences indicated that the voltage-gated potassium channels (Kv) were participated in neuronal damage and microglia function. With the whole cell patch clamp, we found that Meth significantly increased the outward K⁺ currents, therefore, we explored whether Kv1.3, one of the major K⁺ channels expressed in microglia, was involved in Meth-induced microglia damage. Our study showed that Meth significantly increased the cell viability in a dose dependent manner, while the Kv blocker, tetraethylamine (TEA), 4-Aminopyridine (4-AP) and Kv1.3 specific antagonist margatoxin (MgTx), prevented against the damage mediated by Meth. Interestingly, treatment of cells with Meth resulted in increasing expression of Kv1.3 rather than Kv1.5, at both mRNA and protein level, which is partially blocked by MgTx. Furthermore, Meth also stimulated a significant increased expression of IL-6 and TNF-α at protein level, which was significantly inhibited by MgTx. Taken together, these results demonstrated that Kv1.3 was involved in Meth-mediated microglial damage, providing the potential target for the development of therapeutic strategies for Meth abuse.
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Qian
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China ; Departments of Experimental Medicine, Nanjing Drum Tower Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Yu
authors.affiliation: Department of Emergency Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: Key Lab of Modern Toxicology, Ministry of Education. Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xiao
mesh_terms: D015761:4-Aminopyridine / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000818:Animals; D000697:Central Nervous System Stimulants / Q000737:chemistry; D005260:Female; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000378:metabolism; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D008694:Methamphetamine / Q000737:chemistry*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000737:chemistry; D012844:Sincalide; D019789:Tetraethylammonium / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000588:Amines; D000697:Central Nervous System Stimulants; D015850:Interleukin-6; C496975:Kcna3 protein, rat; D051664:Kv1.3 Potassium Channel; D012333:RNA, Messenger; D012604:Scorpion Venoms; D014409:Tumor Necrosis Factor-alpha; D008694:Methamphetamine; C077910:margatoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D012844:Sincalide