ORIGIN OF TETANIC FADE IN ANESTHESIA

描述：(改编自申请者的摘要)非去极化 在手术麻醉过程中使用阻滞剂以产生肌肉 放松一下。然而，他们是否会采取行动仍不确定 突触后或突触前受体产生它们的特征 反复神经刺激后，强直性脊柱炎会消退。褪色可能是由 突触后受体的使用依赖性故障或由于 从突触前终末释放乙酰胆碱。这些研究是 旨在找出突触前和突触前的确切组合 突触后过程在强直性脑萎缩发展中的作用。两个人都- 管库拉林和蛇毒中的阿尔法毒素具有竞争性。 烟碱型乙酰胆碱受体拮抗剂。这很好 确定了d-管库拉林引起的 重复神经刺激期间的终板电流，但矛盾的是 有许多报告表明，阿尔法毒素不会导致 如此褪色。这些发现向一些人表明，d-管库拉林 通过阻断突触前乙酰胆碱受体而导致衰退 通常控制乙酰胆碱的释放。这一理论得到了支持 通过发现阿尔法毒素不会导致褪色，以及通过放射自显影 研究表明，α银环蛇毒素不与 突触前终末。然而，其他研究表明，阿尔法 毒素会引起戏剧性的褪色，就像d-管库拉林一样。申请人的 关于阿尔法毒素影响的相互矛盾的结果的解释 低浓度的毒素会导致褪色，而高浓度的毒素会 而不是因为褪色。因为一些调查人员一直使用HIGH 在他们的实验中，他们错误地认为 阿尔法毒素不会导致褪色。高浓度的毒素可能 有一个额外的效果，可能会抑制褪色的外观。这个 申请者建议检验这一假设，并准确地确定 已知阿尔法毒素的不同浓度所产生的褪色程度 与D-管库拉林相比。

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.