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J Trace Elem Med Biol. 2017 May;41:66-74. doi: 10.1016/j.jtemb.2017.02.011. Epub 2017 Feb 20.

Zn2+ reduction induces neuronal death with changes in voltage-gated potassium and sodium channel currents.

Author information

1
College of Life Sciences, Nankai University, Tianjin 300071, China.
2
Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China.
3
Department of Nutrition, Tianjin Institute of Health and Environmental Medicine, Tianjin 300050, China. Electronic address: jyg1967@126.com.
4
College of Life Sciences, Nankai University, Tianjin 300071, China. Electronic address: liuyanq@nankai.edu.cn.

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 INa activation 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.

KEYWORDS:

Free Zn(2+) deficiency; Neuronal injury; TPEN; Voltage-gated potassium channel current; Voltage-gated sodium channel current

PMID:
28347465
DOI:
10.1016/j.jtemb.2017.02.011
[Indexed for MEDLINE]

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