Beekwilder Jeroen P, Winkelman Daniel L B, van Kempen Gertrudis Th H, van den Berg Rutgeris J, Ypey Dirk L
Department of Neurophysiology, Leiden University Medical Center, Leiden, The Netherlands.
Anesth Analg. 2005 Jun;100(6):1674-1679. doi: 10.1213/01.ANE.0000151162.07211.DD.
To contribute to the understanding of the mechanism underlying selective analgesia by epidural application of suspensions of the local anesthetic butamben (n-butyl-p-aminobenzoate; BAB), we investigated the effect of dissolved BAB on calcium channels in sensory neurons. Small-diameter dorsal root ganglion neurons from newborn mice were used to measure whole-cell barium or calcium currents through calcium channels upon voltage-clamp stimulation. BAB suppressed the voltage-step-evoked barium current of these cells in a concentration-dependent manner with a 50% inhibitory concentration of 207 +/- 14 microM (n = 40). A similar concentration dependency was found for the pharmacologically isolated N-type component of the whole-cell barium current. The time constants of inactivation and deactivation of the N-type current became smaller in the presence of BAB, thus suggesting that kinetic changes are involved in the inhibition of this current. BAB caused a similar inhibition of the total calcium current and its N-type component when these currents were evoked by command potentials with the shape of an action potential. This inhibition of calcium currents by BAB should be considered in the search for the mechanism of selective analgesia by epidural suspensions of this local anesthetic.
为了有助于理解通过硬膜外应用局部麻醉药布坦苯（正丁基 - 对氨基苯甲酸酯；BAB）混悬液实现选择性镇痛的潜在机制，我们研究了溶解的BAB对感觉神经元钙通道的影响。使用新生小鼠的小直径背根神经节神经元，在电压钳刺激下测量通过钙通道的全细胞钡或钙电流。BAB以浓度依赖性方式抑制这些细胞的电压阶跃诱发钡电流，半数抑制浓度为207±14μM（n = 40）。对于全细胞钡电流的药理学分离的N型成分，发现了类似的浓度依赖性。在BAB存在下，N型电流的失活和去激活时间常数变小，因此表明动力学变化参与了该电流的抑制。当这些电流由动作电位形状的指令电位诱发时，BAB对总钙电流及其N型成分产生类似的抑制作用。在探寻这种局部麻醉药硬膜外混悬液选择性镇痛机制时，应考虑BAB对钙电流的这种抑制作用。
