丙泊酚对大鼠心室肌细胞宏观和单通道钠电流的影响。

The effects of propofol on macroscopic and single channel sodium currents in rat ventricular myocytes.

作者信息

Saint D A

机构信息

Department of Physiology, University of Adelaide, SA, Australia.

出版信息

Br J Pharmacol. 1998 Jun;124(4):655-62. doi: 10.1038/sj.bjp.0701876.

DOI:10.1038/sj.bjp.0701876

PMID:9690856

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565436/

Abstract

The effects of the injectable anaesthetic agent propofol (di-isopropyl phenol) were examined on sodium currents and single sodium channels by use of patch-clamp techniques in ventricular myocytes isolated from rat hearts. 2. Propofol dose-dependently blocked the whole cell sodium currents evoked by a voltage step to -30 mV from a holding potential of -90 mV with an EC50 of 14.8+/-2.3 microM (mean+/-s.e.mean). 3. Propofol caused a substantial hyperpolarizing shift in the voltage-dependence of inactivation of sodium currents (168 microM (30 microg ml(-1)) propofol caused a -14 mV shift (P<0.01); 56 microM caused a -8 mV shift (P<0.05)). A smaller shift in the voltage-dependence of activation was produced (4 mV by 168 microM (not statistically significant)), but this was to more depolarized potentials. The maximal sodium conductance, as judged from the activation and inactivation curves, was reduced by 13% by 168 microM propofol (not statistically significant), but propofol did not affect the reversal potential of the current-voltage relationship. 4. The macroscopic rate of inactivation, as measured by the time constant of the exponential fall of current amplitude from the peak current, was also slowed by propofol, from a control time constant of 1.78+/-0.31 ms to 2.93+/-0.47 ms (mean+/-s.e.mean, n=8, P<0.05) by 168 microM propofol. Despite the increase in the time constant, the macroscopic inactivation remained well fitted by a single exponential. The macroscopic rate of activation was also slowed, but to a lesser degree (<10%, not statistically significant) by 168 microM propofol. 5. Propofol slowed the rate of recovery from inactivation of the sodium current, as measured by a two pulse protocol. Propofol (168 microM) increased the time constant of recovery, measured at -100 mV and room temperature, from a control value of 55+/-5.9 ms to 141+/-24.2 ms (mean+/-s.e.mean, n=8, P<0.01). Although the time constant was increased at all voltages measured, the intrinsic voltage-dependence of the rate of recovery was not changed. 6. Single channel recordings showed that the mean open time of single sodium channels was dramatically reduced by propofol (from 0.50+/-0.02 ms in control to 0.28+/-0.01 ms by 56 +/-M propofol and to 0.24+/-0.01 ms by 168 microM, both significantly different from control, P<0.01). Single channel conductance was not changed by either concentration of propofol.

摘要

采用膜片钳技术，在从大鼠心脏分离出的心室肌细胞中，研究了注射用麻醉剂丙泊酚（二异丙基苯酚）对钠电流和单个钠通道的影响。2. 丙泊酚剂量依赖性地阻断了从 -90 mV 的钳制电位到 -30 mV 的电压阶跃所诱发的全细胞钠电流，其半数有效浓度（EC50）为 14.8±2.3 μM（平均值±标准误平均值）。3. 丙泊酚使钠电流失活的电压依赖性发生显著超极化偏移（168 μM（30 μg/ml）丙泊酚导致 -14 mV 的偏移（P<0.01）；56 μM 导致 -8 mV 的偏移（P<0.05））。激活的电压依赖性产生较小的偏移（168 μM 导致 4 mV 的偏移（无统计学意义）），但这是向更去极化的电位偏移。根据激活和失活曲线判断，168 μM 丙泊酚使最大钠电导降低了 13%（无统计学意义），但丙泊酚不影响电流 - 电压关系曲线中的反转电位。4. 通过从峰值电流开始的电流幅度指数下降的时间常数来测量，宏观失活速率也被丙泊酚减慢，168 μM 丙泊酚使对照时间常数从 1.78±0.31 ms 增加到 2.93±0.47 ms（平均值±标准误平均值，n = 8，P<0.05）。尽管时间常数增加，但宏观失活仍能很好地用单指数拟合。宏观激活速率也减慢，但 168 μM 丙泊酚使其减慢程度较小（<10%，无统计学意义）。5. 采用双脉冲方案测量，丙泊酚减慢了钠电流从失活状态恢复的速率。丙泊酚（168 μM）使在 -100 mV 和室温下测量的恢复时间常数从对照值 55±5.9 ms 增加到 141±24.2 ms（平均值±标准误平均值，n = 8，P<0.01）。尽管在所有测量电压下时间常数都增加，但恢复速率的内在电压依赖性未改变。6. 单通道记录显示，丙泊酚显著缩短了单个钠通道的平均开放时间（从对照时的 0.50±0.02 ms 缩短至 56 μM 丙泊酚时的 0.28±0.01 ms 和至 168 μM 时的 0.24±0.01 ms，两者均与对照有显著差异，P<0.01）。两种浓度的丙泊酚均未改变单通道电导。