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    题名: Stimulatory actions of a novel thiourea derivative on large-conductance, calcium-activated potassium channels
    作者: Wu, Sheng‐Nan;Chern, Jyh‐Haur;Shen, Santai;Chen, Hwei‐Hisen;Hsu, Ying‐Ting;Lee, Chih‐Chin;Chan, Ming‐Huan;Lai, Ming‐Chi;Shie, Feng‐Shiun
    詹銘煥
    贡献者: 神科所
    日期: 2017
    上传时间: 2017-07-19 16:25:23 (UTC+8)
    摘要: In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. The effects of compound #326 on Ca2+-activated K+ channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. In pituitary GH3 cells, compound #326 increased the amplitude of Ca2+-activated K+ currents (IK(Ca)) with an EC50 value of 11.6μM, which was reversed by verruculogen, but not tolbutamide or TRAM-34. Under inside-out configuration, a bath application of compound #326 raised the probability of large-conductance Ca2+-activated K+ (BKCa) channels. The activation curve of BKCa channels was shifted to less depolarised potential with no modification of the gating charge of the curve; consequently, the difference of free energy was reduced in the presence of this compound. Compound #326-stimulated activity of BKCa channels is explained by a shortening of mean closed time, despite its inability to alter single-channel conductance. Neither delayed-rectifier nor erg-mediated K+ currents was modified. Compound #326 decreased the peak amplitude of voltage-gated Na+ current with no clear change in the overall current-voltage relationship of this current. In HEK293T cells expressing α-hSlo, compound #326 enhanced BKCa channels effectively. Intriguingly, the inhibitory actions of compound #326 on interleukin 1β in lipopolysaccharide-activated microglia were significantly reversed by verruculogen, whereas BKCa channel inhibitors suppressed the expressions of inducible nitric oxide synthase. The BKCa channels could be an important target for compound #326 if similar in vivo results occur, and the multi-functionality of BKCa channels in modulating microglial immunity merit further investigation. © 2017 Wiley Periodicals, Inc.
    關聯: Journal of Cellular Physiology,
    数据类型: article
    DOI 連結: http://dx.doi.org/10.1002/jcp.25788
    DOI: 10.1002/jcp.25788
    显示于类别:[神經科學研究所] 期刊論文

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