Van den Berg R J, Van Soest P F, Wang Z, Grouls R J, Korsten H H
Laboratory of Physiology, University of Leiden, The Netherlands.
Anesthesiology. 1995 Jun;82(6):1463-73. doi: 10.1097/00000542-199506000-00018.
Aqueous suspensions of the local anesthetic n-butyl-p-aminobenzoate (BAB), epidurally applied in terminal cancer patients, resulted in a sensory blockade, lasting up to several months. To investigate the mechanism of action on the cellular level, the effect of 100 microM BAB on Na+ action potentials and on Na+ currents in dorsal root ganglion neurons from neonatal rats was studied.
Small neurons grown in cell culture were selected for patch-clamp measurements. Both Na+ action potentials, evoked by current pulses of increasing amplitude (current clamp) and Na+ currents, activated at different membrane potentials (voltage clamp), were investigated in the absence and presence of 100 microM BAB. The local anesthetic was applied by external perfusion for 2 or 10 min.
In the presence of 100 microM BAB, either the firing threshold was raised or the action potential was abolished. The maximal peak conductances, underlying the fast sodium current INa,F and the slow sodium current INa,5, were not changed. However, the inactivation of INa,F was increased by BAB. The sigmoid inactivation curve shifted 12 mV toward hyperpolarizing membrane voltages, whereas no changes were found for the inactivation of the slow Na+ current. Only at short exposure times of 2 min, the effects of BAB could be reversed during a 10-min wash-out.
BAB dramatically increased the firing threshold, and in part of the sensory neurons, it blocked the action potential. The inactivation of the fast Na+ channels, but not of the slow Na+ channels, was increased by BAB. Thus, the block of fast Na+ channels by BAB may contribute to epidural analgesia. At exposure times of 10 min, the effect of BAB was not reversible. This probably originates from its high lipid-solubility, which may be an important factor in determining the duration of the block in vivo.
局部麻醉药对氨基苯甲酸正丁酯（BAB）的水混悬液硬膜外应用于晚期癌症患者时，可产生感觉阻滞，持续长达数月。为了在细胞水平上研究其作用机制，研究了100微摩尔/升BAB对新生大鼠背根神经节神经元钠动作电位和钠电流的影响。
选择细胞培养中生长的小神经元进行膜片钳测量。在不存在和存在100微摩尔/升BAB的情况下，研究了由幅度递增的电流脉冲诱发的钠动作电位（电流钳）以及在不同膜电位激活的钠电流（电压钳）。通过外部灌注应用局部麻醉药2或10分钟。
在存在100微摩尔/升BAB的情况下，要么发放阈值升高，要么动作电位被消除。快速钠电流INa,F和缓慢钠电流INa,S的最大峰值电导未改变。然而，BAB增加了INa,F的失活。S形失活曲线向超极化膜电压方向移动了12毫伏，而缓慢钠电流的失活未发现变化。仅在2分钟的短暴露时间下，BAB的作用在10分钟的洗脱过程中可以逆转。
BAB显著提高发放阈值，并且在部分感觉神经元中，它阻断动作电位。BAB增加了快速钠通道的失活，但未增加缓慢钠通道的失活。因此，BAB对快速钠通道的阻断可能有助于硬膜外镇痛。在暴露10分钟时，BAB的作用不可逆转。这可能源于其高脂溶性，这可能是决定体内阻滞持续时间的一个重要因素。
