Leonhardt R, Pekel M, Platt B, Haas H L, Büsselberg D
Institut für Physiologie II, Heinrich-Heine-Universität, Düsseldorf, Germany.
Neurotoxicology. 1996 Spring;17(1):85-92.
The actions of bath applied mercuric chloride (HgCl2) and methylmercury (CH3HgCl) on voltage-activated calcium channel currents (VACCCs) were tested, using the whole cell patch clamp recording technique with cultured dorsal root ganglion (DRG) neurons from 2-4 day old rat pups. Both metal compounds reduced the current irreversibly in a concentration dependent fashion, reaching a new (lower) steady state within 3 to 5 min after application. Inorganic mercury was more effective in reducing the VACCCs with an IC50 of 1.3 microM, while the IC50 for methylmercury was 2.6 microM. But the threshold concentrations were below 0.25 microM for both metal compounds and the calcium channel currents were reduced by more than 90% with concentrations of 5 microM and 20 microM, respectively. The Hill coefficient for both dose-response relationship was calculated as approximately 1. Calcium channel currents were reduced over the entire voltage range, but the current-voltage relation shifted to more positive potentials in a concentration dependent manner, the effect being more pronounced with HgCl2 than with CH3HgCl (1 microM HgCl2: 10 mV shift, 5 microM CH3HgCl: 5 mV shift). At higher concentrations (> or = 2 microM for HgCl2, and > or = 10 microM for CH3HgCl) an unidentified membrane current was observed. The inorganic mercury caused an inward current, while the organic mercury compound generated a biphasic current with a transient inward and a long lasting outward component. Our results suggest that mercury compounds affect the electrical properties of neurons and thereby decrease cognitive and motor performance.
采用全细胞膜片钳记录技术，以2 - 4日龄大鼠幼崽培养的背根神经节（DRG）神经元为研究对象，测试了浴用氯化汞（HgCl2）和甲基汞（CH3HgCl）对电压激活钙通道电流（VACCCs）的作用。两种金属化合物均以浓度依赖性方式不可逆地降低电流，给药后3至5分钟内达到新的（更低的）稳态。无机汞在降低VACCCs方面更有效，IC50为1.3 microM，而甲基汞的IC50为2.6 microM。但两种金属化合物的阈值浓度均低于0.25 microM，且在5 microM和20 microM浓度下，钙通道电流分别降低了90%以上。两种剂量反应关系的希尔系数计算约为1。钙通道电流在整个电压范围内均降低，但电流 - 电压关系以浓度依赖性方式向更正的电位偏移，HgCl2的这种效应比CH3HgCl更明显（1 microM HgCl2：偏移10 mV，5 microM CH3HgCl：偏移5 mV）。在较高浓度下（HgCl2≥2 microM，CH3HgCl≥10 microM），观察到一种不明膜电流。无机汞引起内向电流，而有机汞化合物产生双相电流，包括短暂内向和持久外向成分。我们的结果表明，汞化合物会影响神经元的电特性，从而降低认知和运动能力。
