ACETYLCHOLINE RECEPTOR AND ION CONDUCTANCE MODULATOR SITES AT MURINE NEUROMUSCULAR JUNCTION - EVIDENCE FROM SPECIFIC TOXIN REACTIONS
ACETYLCHOLINE RECEPTOR AND ION CONDUCTANCE MODULATOR SITES AT MURINE NEUROMUSCULAR JUNCTION - EVIDENCE FROM SPECIFIC TOXIN REACTIONS
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DOI：
10.1073/pnas.70.3.949
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发表时间：
1973-01-01
影响因子：
11.1
通讯作者：
WITKOP, B
中科院分区：
文献类型：
--
作者：
ALBUQUER.EX;BARNARD, EA;WITKOP, B
组氨酸毒素的过水衍生物可逆地阻断哺乳动物骨骼肌细胞突触和肌层膜中的兴奋性离子转导系统。乙酰胆碱在神经支配肌肉终板和去神经支配肌肉的结外受体的短暂存在，增加了过氢组氨酸毒素作为突触后膜拮抗剂的作用。α-班加罗毒素和[3H]单乙酰-α-班加罗毒素阻断终板乙酰胆碱受体，两者的结合程度相同。毒虫毒素的作用是部分可逆的。这些电生理结果，再加上过氢组氨酸毒素和/ord-管库碱对[3H]单乙酰-α-班加罗毒素在小鼠膈肌终板结合和班加罗毒素引起的神经肌肉传递不可逆阻断的影响，表明至少有两种类型的位点参与了乙酰胆碱的突触兴奋。一个被班加罗毒素和curare竞争性阻断的位点可能是乙酰胆碱受体。在这一部位结合虫毒是神经肌肉传递的不可逆阻断。第二个位点，被班加罗毒素和过氢组氨酸毒素竞争性阻断，被认为是胆碱能离子电导调节剂的一部分。虫毒与该位点的结合不会导致不可逆的阻滞。
The perhydro derivative of histrionicotoxin reversibly blocks the excitatory ionic transduction system in the synaptic and sarcolemmal membranes of mammalian skeletal muscle cells. The efficacy of perhydrohistrionicotoxin as an antagonist at the post-synaptic membrane is increased by the transient presence of acetylcholine in the endplate of innervated muscles and at extrajunctional receptors in denervated muscles. α-Bungarotoxin and [3H]monoacetyl-α-bungarotoxin block the endplate acetylcholine receptors, each binding to the same extent. The effect of bungarotoxin is partially reversible. These electrophysiological results, together with the effects of perhydrohistrionicotoxin and/ord-tubocurarine on the binding of [3H]monoacetyl-α-bungarotoxin at endplates of murine diaphragm muscle and on the bungarotoxin-elicited irreversible blockade of neuromuscular transmission, suggest that at least two types of sites participate in the synaptic excitation by acetylcholine. One site, competitively blocked by bungarotoxin and by curare, is presumably the acetylcholine receptor. Binding of bungarotoxin at this site is responsible for an irreversible blockade of neuromuscular transmission. The second site, competitively blocked by bungarotoxin and perhydrohistrionicotoxin, is proposed to be part of the cholinergic ion conductance modulator. Binding of bungarotoxin to this site does not result in an irreversible blockade.