Nagasaki M, Komori S, Tamaki H, Ohashi H
Department of Veterinary Science, Faculty of Agriculture, Gifu University, Japan.
Eur J Pharmacol. 1993 Apr 28;235(2-3):197-203. doi: 10.1016/0014-2999(93)90137-7.
The effect of trimebutine on the K+ current in rabbit ileal smooth muscle cells was investigated using the whole-cell patch-clamp technique. Trimebutine (10 microM) inhibited an outward current consisting of a Ca(2+)-dependent K+ current (IKCa) and Ca(2+)-independent K+ current (IKv), elicited by stepping from -80 to -20 mV or more positive. Trimebutine reduced dose dependently the IKv amplitude with an IC50 of 7.6 microM and IKCa amplitude with an IC50 of 23.5 microM. The IKv inhibition was neither voltage- nor use-dependent. Trimebutine (1-100 microM) decreased the amplitude and discharge rate of spontaneous transient outward currents. Trimebutine (30 microM) produced a sustained membrane depolarization of about 10 mV accompanied by a decrease in membrane conductance. The results suggest that the excitatory effects of trimebutine on the gastrointestinal tract may be attributable to the inhibitory action on the K+ current.
采用全细胞膜片钳技术研究了曲美布汀对兔回肠平滑肌细胞钾电流的影响。曲美布汀（10微摩尔）抑制了一种外向电流，该电流由从-80毫伏跃升至-20毫伏或更正电位时引发的钙依赖性钾电流（IKCa）和钙非依赖性钾电流（IKv）组成。曲美布汀剂量依赖性地降低IKv幅度，IC50为7.6微摩尔，降低IKCa幅度，IC50为23.5微摩尔。IKv抑制既不依赖电压也不依赖使用。曲美布汀（1 - 100微摩尔）降低了自发性瞬时外向电流的幅度和发放频率。曲美布汀（30微摩尔）使膜持续去极化约10毫伏，同时伴有膜电导降低。结果表明，曲美布汀对胃肠道的兴奋作用可能归因于对钾电流的抑制作用。
