Referenced in: none

Automatically associated channels: Slo1

Title: Cholesterol metabolite cholestane-3β,5α,6β-triol suppresses epileptic seizures by negative modulation of voltage-gated sodium channels.

Authors: Lipeng Tang, Youqiong Wang, Tiandong Leng, Huanhuan Sun, Yuehan Zhou, Wenbo Zhu, Pengxin Qiu, Jingxia Zhang, Bingzheng Lu, Min Yan, Wenli Chen, Xinwen Su, Wei Yin, Yijun Huang, Haiyan Hu, Guangmei Yan

Journal, date & volume: Steroids, 2015 Jun , 98, 166-72

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25578735

Abstract
Imbalance of excitation and inhibition in neurons is implicated in the pathogenesis of epilepsy. Voltage-gated sodium channels, which play a vital role in regulating neuronal excitability, are one of the major targets for developing anti-epileptic drugs. Here we provide evidence that cholestane-3β,5α,6β-triol (triol), a major metabolic oxysterol of cholesterol, is an effective state-dependent negative sodium channels modulator. Triol reduced Na(+) current density in a concentration-dependent manner. 10 μM triol shifted steady-state/fast/slow inactivation curves of sodium channels toward the hyperpolarizing direction. Additionally, triol reduced voltage-gated sodium currents in a voltage- and frequency-dependent manner. In a kainic acid-induced seizures mouse model, triol (25 mg/kg) significantly increased the latency of seizure onset and attenuated seizure severity. Our findings provide novel insights for understanding the modulatory role of a small molecular oxysterol on voltage-gated sodium channels and suggest triol may represent a novel and promising candidate for epilepsy intervention.