氯非铵对瞬时外向型克隆心脏钾通道电流的一种新增强作用。

A novel enhancing effect of clofilium on transient outward-type cloned cardiac K+ channel currents.

Kobayashi T, Mikala G, Yatani A

Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, OH 45267-0575, USA.

Br J Pharmacol. 1995 Mar;114(6):1222-6. doi: 10.1111/j.1476-5381.1995.tb13336.x.

Abstract

The antiarrythmic drug, clofilium, has been shown to block several types of K+ channel currents. To investigate the effects of clofilium on the transient outward K+ current (Ito), a cloned Ito-type cardiac K+ channel (RHK1) was expressed in Xenopus oocytes and the drug effects were examined on whole cell currents. 2. Extracellular application of clofilium slightly inhibited the current at +60 mV from a holding potential of -80 mV. However, it unexpectedly enhanced the current from a holding potential of -60 mV in a dose-dependent manner (219 +/- 39% of control at 100 microM). 3. This enhancement is probably due to an increase in the ratio of channels in the resting state during steady depolarization, since clofilium shifted the inactivation curve in the depolarizing direction. 4. LY97119, a tertiary ammonium analogue of clofilium, did not exhibit this enhancing effect but only inhibited the current. 5. Clofilium may be useful for the study of channel inactivation because this type of phenomenon has not been reported for any other drug.

摘要

抗心律失常药物氯非铵已被证明可阻断几种类型的钾通道电流。为了研究氯非铵对瞬时外向钾电流（Ito）的影响，在非洲爪蟾卵母细胞中表达了一种克隆的Ito型心脏钾通道（RHK1），并检测了该药物对全细胞电流的影响。2. 从 -80 mV的钳制电位在 +60 mV时，细胞外应用氯非铵会轻微抑制电流。然而，出乎意料的是，它会以剂量依赖的方式增强来自 -60 mV钳制电位的电流（在100 microM时为对照的219 +/- 39%）。3. 这种增强可能是由于在持续去极化过程中静息状态下通道比例增加所致，因为氯非铵使失活曲线向去极化方向移动。4. 氯非铵的叔铵类似物LY97119没有表现出这种增强作用，而只是抑制电流。5. 氯非铵可能有助于通道失活的研究，因为尚未有其他药物报道过此类现象。