摘要
目的研究氯胺酮对大鼠心室肌细胞瞬时外向钾电流(Ito)的影响。方法酶解法分离大鼠心室肌细胞,采用全细胞膜片钳技术记录Ito,观察50μmol/L氯胺酮对Ito电流-电压曲线以及不同浓度氯胺酮对Ito的影响,并研究氯胺酮对Ito通道动力学的影响。结果钳制电压-40mV,刺激电压+70mV条件下,临床相关浓度的氯胺酮50μmol/L使Ito的电流峰值降低23·4%(P<0·01),冲洗后,Ito能够完全恢复。5、10、50、100、500、1000、5000μmol/L的氯胺酮抑制Ito呈浓度依赖性,电流抑制率分别为(13·8±9·7)%、(17·5±6·7)%、(23·4±8·8)%、(31·5±6·7)%、(63·3±5·5)%、(79·7±2·7)%、(88·9±4·4)%,其半数有效浓度(IC50)为299μmol/L。100μmol/L的氯胺酮对激活曲线没有影响;使Ito的失活曲线明显右移,半数失活电压(V1/2)在给药前后数值分别为(-28·27±0·20)mV和(-25·34±0·27)mV(P<0·01),斜率因子(k)值分别为(3·23±0·46)mV和(3·40±0·55)mV(P>0·05)。结论氯胺酮可明显阻滞大鼠心室肌的Ito,这是氯胺酮延长大鼠心室肌动作电位的机理之一,同时氯胺酮使Ito的失活曲线右移。
Objective To study the effect of ketamine on transient outward potassium currents （Ito） in rats ventricle myocytes in order to investigate the mechanisms of prolonged action potential duration by ketamine. Methods Whole-cell patch clamp technique was used to study ho currents in rats ventricle myocytes. Results Ketamine dose-dependently blocked the ho currents evoked by a voltage step from a holding potential of -40 mV to ＋70 mV with a mean IC50 value of 299 μmol/L. Clinically relevant concentration of ketamine （50 μmol/L） reduced ho peak currents by （23.4±8.8） % （P〈0.01）. When ketamine was washed out, ho recovered completely. After the cell exposed to ketamine 100 μmol/L, the steady-state activation curve was not significantly affected; while the steady-state inactivation curve shifted to more depolarized potentials, V1/2 increased from （-28.27± 0. 20） mV to （- 25.34±0.27） mV（P〈0. 01） ,the slope factor （k） was （3.23±0.46） mV and （3.40±0.55） mV in control and drug-used cells respectively. Conclusion Clinically relevant concentration of ketamine significantly inhibit ho currents, which prolonged the action potential.
出处
《临床麻醉学杂志》
CAS
CSCD
2006年第7期528-530,共3页
Journal of Clinical Anesthesiology
关键词
氯胺酮
全细胞膜片钳
大鼠
心室肌
瞬时外向钾电流
Ketamine
Patch clamp technique
Rats
Ventricular myocyte
Transient outward potassium currents
