McLarnon J G, Saint D A, Quastel D M
Mol Pharmacol. 1986 Dec;30(6):631-8.
The effects of dimethyl sulfoxide (DMSO) on subsynaptic response and quantal release of transmitter have been studied at the mammalian neuromuscular junction. Subsynaptically, at low concentrations (up to 1% by volume), DMSO prolongs the time course of decay of miniature endplate currents, (MEPCs), with no significant effect on the amplitude of the currents, which is consistent with an action of DMSO to inhibit acetylcholinesterase. At higher concentrations of DMSO (in excess of 1% by volume) the amplitude of MEPCs and the steady state response to carbamoylcholine (carbachol) are significantly reduced, which suggests an additional action of DMSO other than pure anticholinesterase activity. After pretreatment of the preparation with a low concentration of paraoxon, higher concentrations of DMSO decrease MEPC height and cause highly variable changes in the decay time course of the MEPC. The results suggest that DMSO concentrations in excess of 1% by volume have two distinct and opposite actions on the subsynaptic response; a pure anticholinesterase activity to enhance the response and a depressant effect which is similar to that caused by d-tubocurarine. Presynaptically, DMSO increased both the spontaneous release (measured as the frequency of miniature endplate potentials, fMEPP) and the evoked release (measured as the quantal content of endplate potentials). Both types of release were increased as an exponential function, with the same slope, of the DMSO concentration, suggesting a common mode of action on these two types of release. This action appeared not to be due to an effect on the disposition or effectiveness of calcium ions inside the terminal but, rather, was due to a fusogenic or global effect. In addition, the increase in fMEPP with DMSO was the same when external calcium was replaced by barium. At the concentrations studied, up to 8% by volume, DMSO did not cause any substantial depolarization of the nerve terminal or any appreciable change in the nerve terminal action potential. In a few experiments facilitation was studied at the frog neuromuscular junction and was unchanged by DMSO at concentrations which considerably enhanced transmitter release.
已在哺乳动物神经肌肉接头处研究了二甲基亚砜（DMSO）对突触下反应及递质量子释放的影响。在突触下，低浓度（体积分数高达1%）时，DMSO延长微小终板电流（MEPCs）的衰减时间进程，而对电流幅度无显著影响，这与DMSO抑制乙酰胆碱酯酶的作用一致。在较高浓度的DMSO（体积分数超过1%）时，MEPCs的幅度以及对氨甲酰胆碱（卡巴胆碱）的稳态反应显著降低，这表明DMSO除了具有单纯的抗胆碱酯酶活性外还有其他作用。用低浓度对氧磷预处理标本后，较高浓度的DMSO会降低MEPC高度，并使MEPC的衰减时间进程发生高度可变的变化。结果表明，体积分数超过1%的DMSO对突触下反应有两种截然不同且相反的作用；一种是增强反应的单纯抗胆碱酯酶活性，另一种是类似于d - 筒箭毒碱引起的抑制作用。在突触前，DMSO增加了自发释放（以微小终板电位频率，fMEPP衡量）和诱发释放（以终板电位的量子含量衡量）。两种类型的释放均随DMSO浓度呈指数函数增加，且斜率相同，表明对这两种类型的释放有共同的作用方式。这种作用似乎不是由于对终末内钙离子的分布或有效性有影响，而是由于融合或整体效应。此外，当外部钙离子被钡取代时，DMSO引起的fMEPP增加是相同的。在所研究的浓度下，高达体积分数8%时，DMSO未引起神经终末的任何实质性去极化，也未使神经终末动作电位发生任何明显变化。在一些实验中，在青蛙神经肌肉接头处研究了易化作用，在显著增强递质释放的浓度下，DMSO对其无影响。
