ORIGIN OF TETANIC FADE IN ANESTHESIA

描述：（改编自申请人摘要）非去极化 阻滞剂在手术麻醉期间使用， 放松. 然而，目前还不确定他们是否会采取行动。 突触后或突触前受体，以产生其特征性的 反复神经刺激后强直性痉挛消退。褪色可能是由 突触后受体的使用依赖性失效或突触后受体的减少， 从突触前末梢释放乙酰胆碱。 这些研究 旨在找出突触前和突触后的 突触后过程的发展强直褪色。 两个D- 筒箭毒碱和蛇毒中的α毒素相互竞争 烟碱乙酰胆碱受体拮抗剂。 公 建立了d-筒箭毒碱引起的振幅下降， 终板电流在重复神经刺激，但矛盾的是， 有许多报告表明α毒素不会引起 这样褪色。 这些发现表明，一些d-筒箭毒碱， 通过阻断突触前乙酰胆碱受体， 通常控制乙酰胆碱的释放。 这一理论得到支持 通过发现α毒素不会引起褪色， 研究表明，α银环蛇毒素不会结合到 突触前末梢 然而，其他研究表明，阿尔法 毒素会引起剧烈的褪色就像d-筒箭毒碱一样 申请人的 对α毒素影响的矛盾结果的解释 低浓度的毒素会导致褪色， 不引起褪色。 因为一些调查人员一直使用高 他们错误地认为， 阿尔法毒素不会导致褪色 高浓度的毒素 具有可以抑制褪色出现的附加效果。 的 申请人提出测试该假设并精确地确定 不同浓度的已知α毒素产生的褪色程度 与d-筒箭毒碱相比。

DESCRIPTION: (Adapted from the applicant's abstract) Nondepolarizing blockers are used during surgical anesthesia in order to produce muscle relaxation. However, it is still uncertain whether they act on postsynaptic or presynaptic receptors to produce their characteristic tetanic fade after repetitive nerve stimulation. Fade could be caused by a use dependent failure of postsynaptic receptors or by a decrease in the release of acetylcholine from the presynaptic terminal. These studies are designed to find out the exact combinations of presynaptic and postsynaptic processes in the development of tetanic fade. Both d- tubocurarine and the alpha toxins from snake venom are competitive antagonists at the nicotinic acetylcholine receptor. It is well established that d-tubocurarine causes run down in the amplitude of endplate currents during repetitive nerve stimulation, but paradoxically there are many reports which indicate that the alpha toxins do not cause such fade. These findings have suggested to some that d-tubocurarine causes fade by blocking a presynaptic acetylcholine receptor which normally controls the release of acetylcholine. This theory is supported by the finding that alpha toxins do not cause fade and by autoradiographic studies which show that alpha bungarotoxin does not bind to the presynaptic terminal. However, other studies have indicated that alpha toxins cause dramatic fade just like d-tubocurarine. The applicants' explanation of the contradictory results for the effects of alpha toxins is that low concentrations of toxin cause fade but high concentrations do not cause fade. Because some investigators have consistently used high concentrations of toxin in their experiments, they have wrongly assumed that alpha toxins do not cause fade. High concentrations of toxin could have an additional effect which may suppress the appearance of fade. The applicants propose to test this hypothesis and to exactly determine the degree of fade produced by different concentrations of known alpha toxins in comparison to d-tubocurarine.