Shrivastav B B
J Pharmacol Exp Ther. 1977 Apr;201(1):162-70.
The node of action of ketamine on the nerve membrane has been studied in intact and internally perfused squid giant axons at 10-12 degrees C. Voltage clamp techniques have been employed to measure the maximal values of peak transient and steady-state conductances as an index of activity and to measure the apparent reversal potential for peak transient current. When applied externally to intact axons, kketamine decreased the resting membrane potential, suppressed steady-state conductances and slightly decreased theleakage conductance, although the last effect was not statistically significant. Peak transient conductance was not appreciably affected. However, when the drug was applied internally, both peak transient and steady-state conductances were suppressed. Ketamine applied externally either to intact axons or to internally perfused axons with internal flow temporarily suspended shifted the apparent reversalpotential for peak transient current towards hyperpolarization. The shift was estimated to be 28.5 mV for 200 micronM ketamine. Wahing the intact axons with drug-free sea water shifted the reversal potential further towards membrane hyperploarization. However, internal washing quickly returned the reversal potential to near control value. The change in resting sodium influx caused by external exposure to ketamine was also measured by using radioactive sodium in external sea water at 10 degrees C. Ketamine (200 micronM) changed the resting sodium influx from (28.9 +/- 5.6) x 10(-12 mol/cm2-sec to (41.8 +/- 5.6) x 10(-12 mol/cm2-sec (mean +/- S.E.M.). The data presented in this paper strongly suggest that the shift in the reversal potential for peak current caused by ketamine is due partly to sodium ion accumulation inside the nerve and partly to the increase in the PR/PNa ratio during peak current. These changes would have a profound narcotic effect on the electrical activity of nerve fibers and nerve endings in the brain during ketamine anesthesia.
已在10 - 12摄氏度的完整和内部灌注的鱿鱼巨大轴突中研究了氯胺酮对神经膜的作用位点。采用电压钳技术测量峰值瞬态和稳态电导的最大值作为活性指标，并测量峰值瞬态电流的表观反转电位。当外部施加于完整轴突时，氯胺酮降低静息膜电位，抑制稳态电导，并轻微降低漏电导，尽管最后一个效应无统计学意义。峰值瞬态电导未受到明显影响。然而，当药物内部施加时，峰值瞬态和稳态电导均受到抑制。外部施加于完整轴突或内部灌注且内部流动暂时停止的轴突的氯胺酮，使峰值瞬态电流的表观反转电位向超极化方向移动。对于200微摩尔氯胺酮，该移动估计为28.5毫伏。用无药海水冲洗完整轴突使反转电位进一步向膜超极化方向移动。然而，内部冲洗迅速使反转电位恢复到接近对照值。还通过在10摄氏度的外部海水中使用放射性钠测量了外部暴露于氯胺酮引起的静息钠内流变化。氯胺酮（200微摩尔）使静息钠内流从（28.9±5.6）×10⁻¹²摩尔/平方厘米·秒变为（41.8±5.6）×10⁻¹²摩尔/平方厘米·秒（平均值±标准误）。本文提供的数据强烈表明，氯胺酮引起的峰值电流反转电位的移动部分归因于神经内部的钠离子积累，部分归因于峰值电流期间PR/PNa比值的增加。这些变化在氯胺酮麻醉期间会对脑内神经纤维和神经末梢的电活动产生深远的麻醉作用。
