氯胺酮对人心房肌细胞瞬时外向钾电流的影响

邝素娟 邓春玉 李晓红 刘晓颖 林秋雄 单志新 杨敏 余细勇

氯胺酮对人心房肌细胞瞬时外向钾电流的影响

邝素娟邓春玉李晓红刘晓颖林秋雄单志新杨敏余细勇

Effect of ketamine on transient outward potassium current of isolated human atrial myocytes

KUANG Su-Juan

摘要

摘要:
本研究应用全细胞膜片钳技术观察氯胺酮对人心房肌细胞瞬时外向钾电流 (transient outward potassium current, I_to) 的影响, 以了解其作用的部分机制。标本取自心脏瓣膜置换病人的右心耳, 采用急性酶解法消化分离人心房肌细胞, 室温下以全细胞膜片钳技术记录I_to, 分别观察30、100、300和1 000 µmol·L⁻¹的氯胺酮对I_to的作用。实验过程由pCLAMP 9.0软件程序发放刺激和采集信号并存储于计算机中。结果表明, 氯胺酮对I_to电流-电压曲线呈浓度依赖性抑制作用, 在 +50 mV时, 30、100、300和1 000 µmol·L⁻¹的氯胺酮分别阻断I_to峰电流 (13.62 ± 0.04) %、(38.92 ± 0.05) %、(72.24 ± 0.10) %和 (83.84 ± 0.05) %, 其半数有效浓度 (IC₅₀) 为121 µmol·L⁻¹。但是100 µmol·L⁻¹氯胺酮对I_to的激活和失活曲线以及复活曲线均无明显影响。由此得知, 氯胺酮呈浓度依赖性抑制人心房肌细胞瞬时外向钾电流。

Abstract:
The effects of ketamine on transient outward potassium current (I_to) of isolated human atrial myocytes were investigated to understand the mechanism of part of its effects by whole-cell patch-clamp. Atrial myocytes were enzymatically isolated from specimens of human atrial appendage obtained from patients under going cardiac valve displacing. I_to is recorded in voltage-clamp modes using the patch-clamp technique at room temperature. Currents signals were recorded by an Axopatch 200B amplifier with the Digidata 1322A-pClamp 9.0 data acquisition system. Ketamine decreased I_to of human atrial myocytes in a dose-dependent manner. The current-voltage curve was significantly lowered, 30, 100, 300, and 1 000 µmol·L⁻¹ ketamine decreased respectively I_to current density about (13.62 ± 0.04)%, (38.92 ± 0.05)%, (72.24 ± 0.10)% and (83.84 ± 0.05)% at the potential of 50 mV, with an IC₅₀ of 121 µmol·L⁻¹. The I_to activation curve, inactivation curve and the recovery curve were not altered by ketamine. So, ketamine concentration-dependently decreased I_to of human atrial myocytes.

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