Effect of histrionicotoxin on the ionic conductance modulator of the cholinergic receptor: a quantitative analysis of the end-plate current.

Effect of histrionicotoxin on the ionic conductance modulator of the cholinergic receptor: a quantitative analysis of the end-plate current.
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曲霉毒素对胆碱能受体离子电导调节剂的影响:终板电流的定量分析。

DOI:
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发表时间:
1974
影响因子:
3.5
通讯作者:
J. Daly
J. Daly
中科院分区:
医学2区
文献类型:
--
作者:
E. Albuquerque;K. Kuba;J. Daly

文献摘要

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采用电压钳技术研究了从哥伦比亚蛙Dendrobates histrionicus中分离的毒素histrionicotoxin对蛙缝匠肌的作用。在暴露30分钟后,Histrionicotoxin(3.5 × 10 - 5 M)使终板电流(EPC)的幅度降低到对照的26%,缩短了半衰减时间,但不改变EPC的平衡电位。EPC的半衰减时间的log 10与膜电位之间的关系的斜率降低了20%。终板电导(G EPC)的减少是更大的膜电位变得更负,导致G EPC和膜电位之间的关系滞后。当强直刺激(25 Hz,1秒)应用组蛋白毒素的存在下,前三个EPCs增加(36%),随后的EPCs逐渐下降到40%的第一EPC振幅。EPC振幅的这种下降率随着膜电位变得更负而更大。在破伤风停止后约30秒,EPC振幅恢复。在控制条件下的强直刺激导致EPC的增强。这表明,histrionicotoxin作用于胆碱能受体的离子电导调节剂在其开放的构象,导致减少的G EPC。G EPC的抑制的电位依赖性被解释为不同的受体-离子电导调节剂复合物的构象状态的毒素的差异结合亲和力的表现。
The effect of histrionicotoxin, the toxin isolated from the Colombian frog, Dendrobates histrionicus, was investigated on frog ( Rana pipiens ) sartorius muscles using the voltage clamp technique. After 30 minutes of exposure, histrionicotoxin (3.5 x 10 -5 M) reduced the amplitude of the end-plate current (EPC) to 26% of control, shortened the half decay time, but did not alter the equilibrium potential of the EPC. The slope of the relationship between the log 10 of the half decay time of the EPC and the membrane potential decreased 20%. The reduction of the end-plate conductance ( G EPC ) was greater as the membrane potential became more negative, leading to hysteresis in the relationship between the G EPC and the membrane potential. When tetanic stimulation (25 Hz for 1 second) was applied in the presence of histrionicotoxin, the first three EPCs were augmented (36%) and the subsequent EPCs progressively decreased to 40% of the first EPC amplitude. This rate of decrease in the EPC amplitude was greater as the membrane potential became more negative. The EPC amplitude recovered about 30 seconds after cessation of tetanus. Tetanic stimulation under control conditions resulted in an augmentation of the EPC. It is suggested that histrionicotoxin acts on the ionic conductance modulator of the cholinergic receptor in its open conformation, leading to a reduction of the G EPC . The potential-dependent nature of the suppression of G EPC is interpreted as the manifestation of differential binding affinities of the toxin with different conformational states of the receptor-ionic conductance modulator complex.