Kelly S S, Morgan G P, Smith J W
Br J Pharmacol. 1986 Sep;89(1):47-53. doi: 10.1111/j.1476-5381.1986.tb11119.x.
Intracellular recording, twitch responses and radio-ligand binding techniques were used to study the causes of resistance to (+)-tubocurarine (curare) of extensor digitorum longus (EDL) muscles from dystrophic mice (129 ReJ/strain). The indirectly evoked twitch response of muscles from dystrophic mice was more resistant to block by curare than the twitch response of muscles from normal littermates. The IC50 (concentration producing 50% inhibition of stimulus-evoked contractions) values for the curare block of muscle twitch were 0.78 +/- 0.03 microM and 1.32 +/- 0.05 microM (mean +/- 95% confidence limits) for muscles from normal and dystrophic mice, respectively. There was no difference between muscles from normal and dystrophic mice in the number of alpha-bungarotoxin binding sites per endplate. The amplitudes of both spontaneous miniature endplate potentials (m.e.p.ps) in unblocked preparations and of evoked endplate potentials (e.p.ps) in 1.91 microM curare were greater in muscles from dystrophic mice than in muscles from normal mice. The ratio dystrophic/normal was greater for the e.p.p. amplitudes than for the m.e.p.p. amplitudes. The quantum content of e.p.ps in magnesium-blocked and in cut-fibre preparations was greater in muscles from dystrophic mice than in muscles from normal littermates. Calculation of the binomial parameters n and p in the cut-fibre preparations indicated that this increased quantum content was caused by an increase in the value of p. It is concluded that at least part of the increased resistance to curare of the indirectly evoked twitch response of muscles from dystrophic mice is due to an increase in the quantum content of e.p.ps in these muscles.
采用细胞内记录、抽搐反应和放射性配体结合技术，研究了营养不良小鼠（129 ReJ/品系）趾长伸肌（EDL）对（+）-筒箭毒碱（箭毒）产生抗性的原因。与正常同窝小鼠肌肉的抽搐反应相比，营养不良小鼠肌肉的间接诱发抽搐反应对箭毒阻断的抗性更强。正常和营养不良小鼠肌肉抽搐的箭毒阻断IC50（产生刺激诱发收缩50%抑制的浓度）值分别为0.78±0.03微摩尔和1.32±0.05微摩尔（平均值±95%置信限）。正常和营养不良小鼠肌肉每个终板的α-银环蛇毒素结合位点数量没有差异。在未阻断的制剂中，营养不良小鼠肌肉的自发微小终板电位（m.e.p.ps）幅度和在1.91微摩尔箭毒作用下诱发的终板电位（e.p.ps）幅度均大于正常小鼠肌肉。终板电位幅度的营养不良/正常比值大于微小终板电位幅度的比值。在镁阻断和切断纤维制剂中，营养不良小鼠肌肉的终板电位量子含量高于正常同窝小鼠肌肉。对切断纤维制剂中二项式参数n和p的计算表明，这种增加的量子含量是由p值的增加引起的。得出结论，营养不良小鼠肌肉间接诱发抽搐反应对箭毒抗性增加至少部分是由于这些肌肉中终板电位量子含量的增加。
