Van den Berg R J, Wang Z, Grouls R J, Korsten H H
Department of Physiology and Physiological Physics, University of Leiden, The Netherlands.
Eur J Pharmacol. 1996 Nov 28;316(1):87-95. doi: 10.1016/s0014-2999(96)00638-3.
Effects of the local anesthetic, n-butyl-p-aminobenzoate, at a concentration of 100 microM, were investigated using the whole-cell voltage clamp on dorsal root ganglion neurons cultured from neonatal rat in a serum-enriched medium. During current clamp conditions, the drug either increased the firing threshold or blocked tetrodotoxin-sensitive and tetrodotoxin-resistant Na+ action potentials. These actions were reversible. Under voltage clamp conditions, inactivation of the Na+ current revealed the existence of 3 fast Na+ current components, termed F1, F2 and F3 (tetrodotoxin-sensitive) and 2 slow ones, termed S1 and S2 (tetrodotoxin-resistant). The local anesthetic shifted the midpoint potentials of Na+ inactivation curves for F1, F2 and F3 currents by 7, 21 and 6 mV, respectively, towards hyperpolarizing membrane voltages whereas it did not influence these potentials for the slow currents. The amplitudes of only F3 and S2 currents were reduced by n-butyl-p-aminobenzoate to 24 and 11%, respectively, of their control values. These results show that the local anesthetic has a differential mode of action on the 5 types of Na+ currents, which are apparently present in cultured sensory neurons. This differential action can play an important role in the selective analgesic effect observed after epidural administration of a 10% n-butyl-p-amino-benzoate suspension.
采用全细胞膜片钳技术，在富含血清的培养基中培养新生大鼠背根神经节神经元，研究了浓度为100微摩尔的局部麻醉药对氨基苯甲酸正丁酯的作用。在电流钳制条件下，该药物要么提高放电阈值，要么阻断河豚毒素敏感和河豚毒素耐受的Na⁺动作电位。这些作用是可逆的。在电压钳制条件下，Na⁺电流的失活显示存在3种快速Na⁺电流成分，称为F1、F2和F3（河豚毒素敏感）以及2种慢速成分，称为S1和S2（河豚毒素耐受）。局部麻醉药使F1、F2和F3电流的Na⁺失活曲线的中点电位分别向超极化膜电压方向移动7、21和6毫伏，而对慢速电流的这些电位没有影响。对氨基苯甲酸正丁酯仅使F3和S2电流的幅度分别降低至其对照值的24%和11%。这些结果表明，局部麻醉药对培养的感觉神经元中明显存在的5种Na⁺电流具有不同的作用模式。这种差异作用可能在硬膜外注射10%对氨基苯甲酸正丁酯混悬液后观察到的选择性镇痛作用中起重要作用。
