BLABER L C, BOWMAN W C
Br J Pharmacol Chemother. 1963 Apr;20(2):326-44. doi: 10.1111/j.1476-5381.1963.tb01472.x.
Repetitive discharges recorded from the ventral root and from the gastrocnemius muscle in response to single motor nerve shocks applied close to the muscle after injection of edrophonium, neostigmine or ambenonium were studied in cats anaesthetized with chloralose. Two closely spaced volleys with an interval of 1 to 5 msec between them produced more repetitive firing than did a single shock. With longer intervals, the repetitive firing was not potentiated by the second volley. All frequencies of tetanic stimulation depressed the repetitive firing and, for successive stimuli to produce a degree of repetitive firing equivalent to the first, it was necessary to stimulate at frequencies below 2 shocks/sec. With stimulation frequencies higher than 100 shocks/sec, repetitive firing did not occur unless the duration of the tetanus was shorter than about 30 msec when slight repetition followed the last stimulus of the train. With stimulation frequencies of 100 down to 20 shocks/sec, repetitive firing was produced only by the first volley of the tetanus. Subsequent nerve action potentials of the tetanus occurring during the repetitive firing in the nerve following the first volley were partially extinguished by collision with the back discharge. This effect contributed to the waning tetanus, which is characteristic of treatment with an anticholinesterase, but the main depression of tetanic contractions appeared to be a consequence of depolarization block through accumulating acetylcholine. Tubocurarine and benzoquinonium reversed the initial "extinction" phase of the depressed tetani by abolishing the repetitive discharge in the nerve and in larger doses reversed the secondary depressant phase presumably by reducing the excessive end-plate depolarization. The results are discussed in relation to the hypothesis that anticholinesterases may effect transmission by acting at three sites at the neuromuscular junction-on acetylcholinesterase, at the motor nerve ending and at the motor end-plate-and that reaction at any one site may be augmented by the production of reverberating activity across the junction.
在用氯醛糖麻醉的猫身上，研究了在注射依酚氯铵、新斯的明或氨甲酰胆碱后，对靠近肌肉处施加的单个运动神经电刺激，记录到的腹根和腓肠肌的重复放电情况。两个间隔为1至5毫秒的紧密排列的群集电刺激比单个电刺激产生更多的重复放电。间隔时间更长时，第二个群集电刺激不会增强重复放电。所有频率的强直刺激都会抑制重复放电，并且，为了使连续刺激产生与第一次相同程度的重复放电，有必要以低于每秒2次的频率进行刺激。当刺激频率高于每秒100次时，除非强直收缩的持续时间短于约30毫秒，即强直刺激的最后一个刺激之后会有轻微重复，否则不会出现重复放电。当刺激频率从每秒100次降至20次时，只有强直刺激的第一个群集电刺激会产生重复放电。在第一个群集电刺激后神经重复放电期间出现的强直刺激的后续神经动作电位，会因与反向放电碰撞而部分消失。这种效应导致了强直收缩减弱，这是抗胆碱酯酶治疗的特征，但强直收缩的主要抑制似乎是由于乙酰胆碱积累导致的去极化阻滞。筒箭毒碱和苯醌铵通过消除神经中的重复放电，逆转了抑制性强直收缩最初的“消失”阶段，大剂量时大概通过减少终板过度去极化，逆转了继发性抑制阶段。结合抗胆碱酯酶可能通过作用于神经肌肉接头的三个部位——乙酰胆碱酯酶、运动神经末梢和运动终板——来影响传递的假说，以及在任何一个部位的反应可能因跨接头产生的回响活动而增强的假说，对这些结果进行了讨论。
