title: Zn2+reduction induces neuronal death with changes in voltage-gated potassium and sodium channel currents.
abstract: In the present study, cultured rat primary neurons were exposed to a medium containing N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a specific cell membrane-permeant Zn2+chelator, to establish a model of free Zn2+deficiency in neurons. The effects of TPEN-mediated free Zn2+ion reduction on neuronal viability and on the performance of voltage-gated sodium channels (VGSCs) and potassium channels (Kvs) were assessed. Free Zn2+deficiency 1) markedly reduced the neuronal survival rate, 2) reduced the peak amplitude of INa, 3) shifted the INaactivation curve towards depolarization, 4) modulated the sensitivity of sodium channel voltage-dependent inactivation to a depolarization voltage, and 5) increased the time course of recovery from sodium channel inactivation. In addition, free Zn2+deficiency by TPEN notably enhanced the peak amplitude of transient outward K+currents (IA) and delayed rectifier K+currents (IK), as well as caused hyperpolarization and depolarization directional shifts in their steady-state activation curves, respectively. Zn2+supplementation reversed the effects induced by TPEN. Our results indicate that free Zn2+deficiency causes neuronal damage and alters the dynamic characteristics of VGSC and Kv currents. Thus, neuronal injury caused by free Zn2+deficiency may correlate with its modulation of the electrophysiological properties of VGSCs and Kvs.
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tian
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: He
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Hui-Nan
authors.initials: HN
authors.lastname: Xu
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Di
authors.initials: D
authors.lastname: An
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Heng
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.affiliation: Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China. Electronic address: jyg1967@126.com.
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Jiang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: liuyanq@nankai.edu.cn.
authors.forename: Yan-Qiang
authors.initials: YQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D005029:Ethylenediamines / Q000008:administration & dosage / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000378:metabolism*; D015032:Zinc / Q000008:administration & dosage / Q000172:deficiency* / Q000494:pharmacology*
chemical_list: D005029:Ethylenediamines; D015221:Potassium Channels; D015222:Sodium Channels; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
keywords: Free Zn(2+) deficiency; Neuronal injury; TPEN; Voltage-gated potassium channel current; Voltage-gated sodium channel current