Methylmercury-induced depression of neuromuscular transmission in the rat.
Methylmercury-induced depression of neuromuscular transmission in the rat.
复制标题
甲基汞诱导大鼠神经肌肉传递抑制。
作者：
W. Atchison;T. Narahashi
采用常规微电极记录技术，观察了甲基汞浴对成年雄性大鼠离体膈神经-横隔膜神经肌肉传递的影响。在20和100微米的浓度下，甲基汞使微型终板电位(MEPP)的频率从对照的0.3-0.8/秒增加到1.5-35/秒。MEPP频率在暴露于20微米后15-40分钟和暴露于100微米甲基汞后5-15分钟出现增加。在4微米的浓度下，甲基汞并没有增加MEPP的频率，事实上，略有降低。在正常的钙离子和镁离子浓度(分别为2 mM和1 mM)下，MEPP频率的增加比低钙离子和高镁离子(分别为1 mM和8 mM)时发生的更快，幅度更小，尽管在每种情况下，MEPP频率都显著增加。甲基汞引起的自发神经递质释放增加不能被1微米河豚毒素逆转。不同浓度的甲基汞对MEPP波幅无明显影响。在量子含量减少的条件下(1 mM Ca~(2+)和8 mM Mg~(2+))诱发的终板电位(EPPS)幅度降低，最后被20微米和100微米甲基汞所阻断，但不被4微米甲基汞所阻断。20微米甲基汞作用30~40分钟后出现EPP阻断，100微米甲基汞作用4~5分钟后阻断。在EPP阻断时，仍可观察到大小正常的MEPP。在暴露于100微米甲基汞的20-30分钟内，应用ACh产生的终板去极化的幅度保持不变。较高浓度的甲基汞显著降低了神经递质释放的量子含量和神经递质的即刻储存量，同时增加了神经递质的释放概率。不同浓度的甲基汞对肌纤维的静息膜电位无明显影响。用无药物溶液洗涤1小时后，甲基汞的作用不可逆。这表明，急性甲基汞中毒不可逆转地改变哺乳动物神经肌肉接头的突触前功能。
Effects of bath applied methylmercury on neuromuscular transmission were assessed in the isolated phrenic nerve-hemidiaphragm of adult male rats using conventional microelectrode recording techniques. At concentrations of 20 and 100 microM, methylmercury increased the frequency of miniature end-plate potentials (MEPPs) from control values of 0.3-0.8/sec to 1.5-35/sec. An increase in MEPP frequency occurred after 15-40 min of exposure to 20 microM, and 5-15 min after exposure to 100 microM methylmercury. At a concentration of 4 microM, methylmercury did not increase MEPP frequency, and in fact, slightly decreased it. The increase in MEPP frequency occurred more rapidly and was smaller in magnitude with normal Ca2+ and Mg2+ concentrations (2 mM and 1 mM, respectively) than with low Ca2+ and high Mg2+ (1 mM and 8 mM, respectively) in the bathing solution, although in each case, significant increases in MEPP frequency were observed. The increase in spontaneous neurotransmitter release caused by methylmercury was not reversed by treatment with 1 microM tetrodotoxin. MEPP amplitude was not significantly altered by any concentration of methylmercury tested. End-plate potentials (EPPs) evoked under conditions of diminished quantal content (1 mM Ca2+ and 8 mM Mg2+) were decreased in amplitude, and finally blocked by 20 microM and 100 microM methylmercury, but not by 4 microM methylmercury. EPP block occurred after 30-40 min with 20 microM methylmercury, and after 4-5 min with 100 microM methylmercury. At the time of EPP block, MEPPs of normal size were still observed. The amplitude of end-plate depolarizations produced by iontophoretic application of ACh remained constant during 20-30 min of exposure to 100 microM methylmercury. Quantal content of transmitter release and the immediately available store of neurotransmitter were drastically reduced by higher concentrations of methylmercury, while the probability of release was increased. Resting membrane potentials of muscle fibers were not altered significantly by any concentration of methylmercury tested. The observed effects of methylmercury were not reversible upon washing with drug free solution for one hour. It is suggested that acute methylmercury poisoning irreversibly alters presynaptic function at the mammalian neuromuscular junction.