Fu W M, Liu C Y, Lin-Shiau S Y
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, R.O.C.
Arch Int Pharmacodyn Ther. 1988 Sep-Oct;295:52-66.
Both Hg2+ and CH3Hg+ exert a depressive action on the twitch amplitude elicited by nerve stimulations more rapidly than that by muscle stimulation. CH3Hg+ was relatively more potent than Hg2+ in the nerve depressive action but was weaker on the muscle. Hg2+ induced a rapid phase and a slow phase of contracture in the diaphragm, while CH3Hg+ induced only a slow one. The biphasic contracture induced by Hg2+ could be inhibited by repetitive washout of the diaphragm with low Ca2+ (10(-3) mM) Krebs and also by treatment with glycerol to close T-tubule, while the slow contracture induced by CH3Hg+ was little affected by glycerol treatment. None of denervation, d-tubocurarine and tetrodotoxin inhibited the contracture induced by Hg2+ and CH3Hg+, indicating that the contracture was induced by a direct action on the muscle. Hg2+, but not CH3Hg+, rapidly caused a decrease of the membrane potential, decreased the amplitude and prolonged the duration of the muscle action potential. Hg2+ also initially decreased and then increased 45Ca2+ uptake of the diaphragm, but CH3Hg+ had no effect, except a prolonged incubation at a high concentration. The action of Hg2+ could be antagonized by glutathione, and CH3Hg+ was more susceptible than Hg2+ to the antagonistic action of glutathione. Both Hg2+ and CH3Hg+ did not change the ATP content of the diaphragm. All of these findings indicate that the monovalent organic CH3Hg+, with a higher lipophilicity, possesses a higher affinity to the nerve while the divalent cationic Hg2+ exerted more effects than CH3Hg+ on the sarcolemma of the mouse diaphragm.
Hg2+和CH3Hg+对神经刺激引发的抽搐幅度产生抑制作用的速度比肌肉刺激引发的更快。在神经抑制作用方面,CH3Hg+比Hg2+相对更有效,但对肌肉的作用较弱。Hg2+在膈肌中诱导出快速相和缓慢相的挛缩,而CH3Hg+仅诱导出缓慢相的挛缩。Hg2+诱导的双相挛缩可通过用低钙(10(-3) mM)的Krebs溶液反复冲洗膈肌以及用甘油处理以封闭T小管来抑制,而CH3Hg+诱导的缓慢挛缩几乎不受甘油处理的影响。去神经、d -筒箭毒碱和河豚毒素均未抑制Hg2+和CH3Hg+诱导的挛缩,表明该挛缩是由对肌肉的直接作用引起的。Hg2+能迅速导致膜电位下降,降低肌肉动作电位的幅度并延长其持续时间,但CH3Hg+则无此作用。Hg2+最初还会使膈肌的45Ca2+摄取量先减少后增加,但CH3Hg+除了在高浓度下长时间孵育外没有影响。Hg2+的作用可被谷胱甘肽拮抗,且CH3Hg+比Hg2+对谷胱甘肽的拮抗作用更敏感。Hg2+和CH3Hg+均未改变膈肌的ATP含量。所有这些发现表明,具有较高亲脂性的一价有机CH3Hg+对神经具有更高的亲和力,而二价阳离子Hg2+对小鼠膈肌的肌膜产生的影响比CH3Hg+更大。