Lin J H, Rydqvist B
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Acta Physiol Scand. 1999 May;166(1):65-74. doi: 10.1046/j.1365-201X.1999.00525.x.
The effect of the local anaesthetics lidocaine, its meta-isomer, LL33, bupivacaine, tetracaine and procaine on the transducer properties of the stretch receptor neurone of the crayfish Pacifastacus leniusculus was investigated using a two microelectrode voltage clamp. Lidocaine increased the receptor current whereas LL33, bupivacaine and tetracaine reduced the receptor current in a reversible dose-dependent way. Procaine did not affect the receptor responses. The onset of the effect was generally slow in the order of minutes. Lidocaine increased the conductance of the mechanotransducer 50 +/- 7% (mean +/- SD, n = 4) and changed the reversal potential -8 +/- 1 mV (mean +/- SEM, n = 8), which indicates a major K+ conductance increase through the mechanosensitive channels. The other local anaesthetics increase the K+ conductance of the mechanotransducer without increasing the total conductance, which suggests that only P(Na)/P(K) is changed. These substances seem to have a Ca2+ dependent effect on the gating properties of the mechanosensitive channels in addition to their effect on the permeability through the channels as compared with lidocaine. All local anaesthetics investigated decreased the leak conductance of the receptor neurone. The effects of local anaesthetics on the mechanosensitive channels whether activating or blocking is correlated to the oil:water distribution coefficients and their relative hydrophobicity/hydrophilicity ratio. The results are consistent with the hypothesis that the local anaesthetic effect is mediated by changes in the lipid phase of the membrane.
使用双微电极电压钳研究了局部麻醉剂利多卡因、其间位异构体LL33、布比卡因、丁卡因和普鲁卡因对小龙虾美洲螯龙虾牵张感受器神经元换能特性的影响。利多卡因增加了感受器电流，而LL33、布比卡因和丁卡因则以可逆的剂量依赖性方式降低了感受器电流。普鲁卡因不影响感受器反应。效应的起效通常较慢，以分钟计。利多卡因使机械换能器的电导增加了50±7%（平均值±标准差，n = 4），并使反转电位改变了-8±1 mV（平均值±标准误，n = 8），这表明通过机械敏感通道的主要钾电导增加。其他局部麻醉剂增加了机械换能器的钾电导，但没有增加总电导，这表明仅P(Na)/P(K)发生了变化。与利多卡因相比，这些物质似乎除了对通道通透性有影响外，还对机械敏感通道的门控特性有钙依赖性作用。所有研究的局部麻醉剂均降低了感受器神经元的漏电导。局部麻醉剂对机械敏感通道的作用，无论是激活还是阻断，都与油：水分配系数及其相对疏水/亲水性比率相关。结果与局部麻醉作用是由膜脂质相变化介导的这一假设一致。
