Stimulatory actions of a novel thiourea derivative on large-conductance, calcium-activated potassium channels

Sheng Nan Wu, Jyh Haur Chern, Santai Shen, Hwei Hisen Chen, Ying Ting Hsu, Chih Chin Lee, Ming Huan Chan, Ming Chi Lai, Feng Shiun Shie

研究成果: Article同行評審

38 引文 斯高帕斯(Scopus)

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 11.6 μM, 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.

原文English
頁(從 - 到)3409-3421
頁數13
期刊Journal of Cellular Physiology
232
發行號12
DOIs
出版狀態Published - 2017 12月

All Science Journal Classification (ASJC) codes

  • 生理學
  • 臨床生物化學
  • 細胞生物學

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