当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > Cholestane-3β, 5α, 6β-triol suppresses neuronal hyperexcitability via binding to voltage-gated sodium channels.

Cholestane-3β, 5α, 6β-triol suppresses neuronal hyperexcitability via binding to voltage-gated sodium channels.

Abstract：

:Neuronal hyperexcitability is identified as a critical pathological basis of epileptic seizures. Cholestane-3β, 5α, 6β-triol (Triol) is a major metabolic oxysterol of cholesterol. Although its neuroprotective effect on ischemia-induced neuronal injury and negative modulation of voltage-gated sodium (Nav) channels were well established, the physical binding site of triol to sodium channels and its effects on neuronal hyperexcitability have not yet been explored. In this study, we utilized molecular docking and molecular dynamics simulation to investigate the interaction between triol and Nav Channels. Our results demonstrated that triol binds to the indole ring of Trp122 of the Nav Channel in silico with a high biological affinity. We further found that triol negatively modulates the action potentials bursts of hippocampal neurons by cell-attached patch recording. Moreover, triol significantly inhibits low Mg2+-induced hyperexcitability in vitro. In addition, triol attenuates pentylenetetrazole (PTZ)-induced convulsive-form behavioral deficits in vivo. Together, our results suggest that triol suppresses neuronal hyperexcitability via binding to Nav channel, indicating that triol might be an attractive lead compound for the treatment of neuronal hyperexcitability-related neurological disorders, especially epileptic seizures.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Tang L,Yan M,Leng T,Yin W,Cai S,Duan S,Zhu W,Lin S,Huang J,Yan G,Zheng G,Chen Y

doi

10.1016/j.bbrc.2018.01.004

subject

Has Abstract

pub_date

2018-01-29 00:00:00

pages

95-100

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)30004-4

journal_volume

496

pub_type

杂志文章

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