Poyraz Deniz, Bräu Michael E, Wotka Friederike, Puhlmann Birgit, Scholz Andreas M, Hempelmann Gunter, Kox Wolfgang J, Spies Claudia D
*Department of Anesthesiology and Intensive Care Medicine, University Hospital Charité Campus Mitte, Humboldt University, Berlin, Germany; †Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital, Justus-Liebig-University, Giessen, Germany; and ‡Department of Physiology, Justus-Liebig-University, Giessen, Germany.
Anesth Analg. 2003 Nov;97(5):1317-1324. doi: 10.1213/01.ANE.0000082243.98617.3B.
Local anesthetics and alcohols block impulse conduction in peripheral nerves by inhibiting Na(+) currents. In small peripheral nerve fibers, tetrodotoxin-resistant (TTX-r) Na(+) channels play an important role in impulse generation. We investigated the effects of lidocaine and the alcohol octanol on TTX-r Na(+) channels. Currents were recorded with the whole-cell patch-clamp method from enzymatically isolated rat dorsal root ganglion cells (data evaluation: nonlinear least-squares fitting). Lidocaine and octanol blocked the TTX-r Na(+) current in a reversible and concentration-dependent manner (50% inhibitory concentration values: 177 +/- 25 and 455 +/- 25 microM, respectively). Lidocaine additionally produced a strong use-dependent block. Both drugs showed a strong dynamic block (i.e., block developed during the time course of current activation and inactivation). Double-pulse protocols showed a slow dissociation of lidocaine from the channel during repolarization (time constant: 1763 +/- 63 ms; 300 microM). The dissociation of octanol was too quick to be distinguished from normal current repriming kinetics of 2.2 ms. Lidocaine and octanol acted noncompetitively in the Na(+) channel. Lidocaine and octanol have different blocking properties on the TTX-r Na(+) current and bind to different channel sites.
Lidocaine and octanol have different inhibitory effects on the function of tetrodotoxin-resistant Na(+) channels in rat dorsal root ganglion cells, as well as noncompetitive modes of action, as investigated by the whole-cell patch-clamp method, and therefore are likely to have different binding sites on the channel.
局部麻醉药和酒精通过抑制钠离子电流来阻断外周神经的冲动传导。在小型外周神经纤维中，河豚毒素抗性（TTX-r）钠离子通道在冲动产生中起重要作用。我们研究了利多卡因和酒精辛醇对TTX-r钠离子通道的影响。采用全细胞膜片钳技术记录酶分离的大鼠背根神经节细胞的电流（数据评估：非线性最小二乘法拟合）。利多卡因和辛醇以可逆且浓度依赖性方式阻断TTX-r钠离子电流（50%抑制浓度值分别为177±25和455±25微摩尔）。利多卡因还产生强烈的使用依赖性阻断。两种药物均表现出强烈的动态阻断（即，在电流激活和失活过程中产生阻断）。双脉冲方案显示，复极化期间利多卡因从通道缓慢解离（时间常数：1763±63毫秒；300微摩尔）。辛醇的解离太快，无法与2.2毫秒的正常电流再激活动力学区分开来。利多卡因和辛醇在钠离子通道中起非竞争性作用。利多卡因和辛醇对TTX-r钠离子电流具有不同的阻断特性，并结合到不同的通道位点。
通过全细胞膜片钳技术研究发现，利多卡因和辛醇对大鼠背根神经节细胞中河豚毒素抗性钠离子通道的功能具有不同的抑制作用，以及非竞争性作用模式，因此它们可能在通道上具有不同的结合位点。
