汞诱导小鼠膈肌肌强直的研究。
Studies on mercury-induced myotonia in the mouse diaphragm.
作者信息
Liu S H, Lin-Shiau S Y
机构信息
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Republic of China.
出版信息
Arch Int Pharmacodyn Ther. 1992 Sep-Oct;319:86-100.
Muscle contracture and myotonia of mouse diaphragm, induced by HgCl2, were studied. HgCl2 induced myotonia of mouse diaphragm only on condition that the Hg2+ contracture was inhibited by 0.005-0.01 mM NaCN. A higher concentration of 0.05 mM NaCN abolished both the Hg2+ contracture and Hg2+ myotonia. This finding suggests that the Hg2+ contracture masked the Hg2+ myotonia which was less sensitive to the inhibitory action of NaCN. This differential inhibitory action of NaCN on Hg2+ contracture from Hg2+ myotonia implies a possibility that NaCN antagonized the actions of HgCl2 not only through a simple chemical interaction. Hg2+ myotonia was characterized by an increase in contractile amplitude and a prolongation of contractile duration which were associated with stimulus-bound repetitive action potentials and an increase in membrane input resistance. A low Cl- medium as well as a Cl- channel blocker (9-anthracene carboxylic acid) not only by themselves induced myotonia, but also antagonized Hg2+ myotonia. Thus, Hg2+ appeared to mimic the Cl- channel blocker in inducing myotonia through a blockade of the Cl- channel. K+ channel blockers (4-aminopyridine, uranyl nitrate and tetraethylammonium chloride), as well as low (0.25 mM) Ca2+ Krebs, augmented Hg2+ myotonia while ATP-sensitive K+ channel blockers (tolbutamide and glibenclamide) antagonized Hg2+ myotonia (in the presence of NaCN). Since glibenclamide did not affect myotonia induced by a Cl- channel blocker, it was suggested that glibenclamide inhibited the Hg2+ myotonia through an interaction either directly or indirectly with NaCN on the sarcolemma. All of these findings suggest that K+ channels (delayed rectifier and Ca(2+)-activated K+ channel) functionally cooperated with the Cl- channel of the sarcolemma in the regulation of the skeletal muscle contraction. In this study, K+ channel blockers synergistically cooperated with Cl- channel blockers in inducing myotonia of the mouse diaphragm, while an ATP-sensitive K+ channel blocker exerted only an opposite effect on NaCN. Ca2+ appeared to play an important role in regulating the ionic channel activities, especially the Cl- channel, since low Ca2+ markedly potentiated not only Hg2+ but also low Cl- in inducing myotonia.
研究了由氯化汞（HgCl₂）诱导的小鼠膈肌肌肉挛缩和肌强直。仅在0.005 - 0.01 mM的氰化钠（NaCN）抑制Hg²⁺挛缩的条件下，HgCl₂才会诱导小鼠膈肌出现肌强直。0.05 mM的较高浓度NaCN会消除Hg²⁺挛缩和Hg²⁺肌强直。这一发现表明，Hg²⁺挛缩掩盖了对NaCN抑制作用不太敏感的Hg²⁺肌强直。NaCN对Hg²⁺挛缩和Hg²⁺肌强直的这种差异抑制作用意味着，NaCN拮抗HgCl₂的作用不仅是通过简单的化学相互作用。Hg²⁺肌强直的特征是收缩幅度增加和收缩持续时间延长，这与刺激相关的重复动作电位以及膜输入电阻增加有关。低Cl⁻培养基以及Cl⁻通道阻滞剂（9 - 蒽甲酸）不仅自身会诱导肌强直，还会拮抗Hg²⁺肌强直。因此，Hg²⁺似乎通过阻断Cl⁻通道在诱导肌强直方面模拟了Cl⁻通道阻滞剂的作用。钾（K⁺）通道阻滞剂（4 - 氨基吡啶、硝酸铀酰和氯化四乙铵）以及低（0.25 mM）Ca²⁺的克雷布斯液会增强Hg²⁺肌强直，而ATP敏感性K⁺通道阻滞剂（甲苯磺丁脲和格列本脲）会拮抗Hg²⁺肌强直（在存在NaCN的情况下）。由于格列本脲不影响由Cl⁻通道阻滞剂诱导的肌强直，因此表明格列本脲通过直接或间接与肌膜上的NaCN相互作用来抑制Hg²⁺肌强直。所有这些发现表明，K⁺通道（延迟整流钾通道和Ca²⁺激活的K⁺通道）在骨骼肌收缩调节中与肌膜的Cl⁻通道在功能上相互协作。在本研究中，K⁺通道阻滞剂与Cl⁻通道阻滞剂在诱导小鼠膈肌肌强直方面协同作用，而ATP敏感性K⁺通道阻滞剂对NaCN仅产生相反的作用。Ca²⁺似乎在调节离子通道活性，尤其是Cl⁻通道方面起重要作用，因为低Ca²⁺不仅在诱导肌强直方面显著增强了Hg²⁺的作用，还增强了低Cl⁻的作用。
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