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Stimulatory actions of a novel thiourea derivative on large‐conductance, calcium‐activated potassium channels
Author(s) -
Wu ShengNan,
Chern JyhHaur,
Shen Santai,
Chen HweiHisen,
Hsu YingTing,
Lee ChihChin,
Chan MingHuan,
Lai MingChi,
Shie FengShiun
Publication year - 2017
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25788
Subject(s) - chemistry , calcium activated potassium channel , bk channel , biophysics , patch clamp , conductance , inward rectifier potassium ion channel , potassium channel , sk channel , gating , ion channel , electrophysiology , membrane potential , stereochemistry , biochemistry , receptor , medicine , biology , physics , condensed matter physics
In this study, we examine whether an anti‐inflammatory thiourea derivative, compound #326, actions on ion channels. The effects of compound #326 on Ca 2+ ‐activated K + channels were evaluated by patch‐clamp recordings obtained in cell‐attached, inside‐out or whole‐cell configuration. In pituitary GH 3 cells, compound #326 increased the amplitude of Ca 2+ ‐activated K + currents ( I K(Ca) ) with an EC 50 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 Ca 2+ ‐activated K + (BK Ca ) channels. The activation curve of BK Ca 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 BK Ca 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 BK Ca channels effectively. Intriguingly, the inhibitory actions of compound #326 on interleukin 1β in lipopolysaccharide‐activated microglia were significantly reversed by verruculogen, whereas BK Ca channel inhibitors suppressed the expressions of inducible nitric oxide synthase. The BK Ca channels could be an important target for compound #326 if similar in vivo results occur, and the multi‐functionality of BK Ca channels in modulating microglial immunity merit further investigation.