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线虫寄生虫猪蛔虫神经肌肉传递的生理学和药理学。

The physiology and pharmacology of neuromuscular transmission in the nematode parasite, Ascaris suum.

作者信息

Martin R J, Pennington A J, Duittoz A H, Robertson S, Kusel J R

机构信息

Department of Pre-clinical Veterinary Sciences, University of Edinburgh.

出版信息

Parasitology. 1991;102 Suppl:S41-58. doi: 10.1017/s0031182000073285.

DOI:10.1017/s0031182000073285
PMID:1647516
Abstract

The organization of Ascaris motoneurones and nervous system is summarized. There is an anterior nerve ring and associated ganglia, main dorsal and ventral nerve cords which run longitudinally, and a small set of posterior ganglia. Cell bodies of motoneurones are found in the ventral nerve cord and occur in 5 repeating 'segments'; each contains 11 motoneurones. Seven morphological types of excitatory or inhibitory motoneurone are recognized. Each Ascaris somatic muscle cell is composed of the contractile spindle; the bag region, containing the nucleus; the arm; and the syncytial region, the location of neuromuscular junctions. The resting membrane potential of muscle is approximately -30 mV and shows regular depolarizing, Ca-dependent 'spike potentials' superimposed on smaller Na(+)- and Ca2(+)-dependent 'slow waves' and even slower 'modulation waves'. The membrane shows high Cl- permeability. Adjacent cells are electrically coupled so that electrical activity in the cells is synchronized. Acetylcholine (ACh) and gamma-aminobutyric acid (GABA) affect the electrical activity. Bath-applied ACh increases membrane cation conductance, depolarizes the cells, alters the frequency and amplitude of spike potentials and produces contraction. Bath-applied GABA increases Cl- conductance, decreases spike activity and causes hyperpolarization and muscle relaxation. The extra-synaptic ACh receptors on the bag region of Ascaris muscle can be regarded as a separate subtype of nicotinic receptor. ACh and anthelmintic agonists (pyrantel, morantel, levamisole) produce a dose-dependent increase in cation conductance and membrane depolarization which is blocked by tubocurarine, mecamylamine but not by hexamethonium. The potency of GABA agonists, with the exception of sulphonic acid derivatives, correlates with the vertebrate GABAa receptor. The potency of antagonists does not. Thus, bicuculline, securinine, pitrazepine, SR95531 and RU5135 are potent vertebrate GABAa antagonists but have little effect on GABA receptors. The potency order of the arylaminopyridazine GABA antagonists: SR95103, SR95132, SR42666, SR95133, SR95531, SR42627 and SR42640 at the Ascaris GABA receptors contrasts with that at vertebrate GABAa receptors. It has been suggested that the receptor is referred to as a GABAn receptor. Patch-clamp studies show that ACh activates a non-selective cation channel which has a main conductance of 40-50pS and apparent mean open time of 1.3 ms; a smaller channel of 20-30 pS with a similar open-time is also activated. Pyrantel and levamisole also produce openings with similar conductances and open-times.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

本文总结了蛔虫运动神经元和神经系统的组织架构。蛔虫有一个前部神经环及相关神经节、纵向延伸的主要背侧和腹侧神经索,以及一小群后部神经节。运动神经元的细胞体位于腹侧神经索中,呈5个重复的“节段”排列;每个节段包含11个运动神经元。已识别出7种形态类型的兴奋性或抑制性运动神经元。每条蛔虫的体肌细胞由收缩纺锤体、含细胞核的袋状区域、臂以及神经肌肉接头所在的合胞体区域组成。肌肉的静息膜电位约为 -30 mV,并呈现出规则的去极化现象,叠加在较小的钠(Na⁺)和钙(Ca²⁺)依赖性“慢波”以及更慢的“调制波”上的是钙依赖性“锋电位”。该膜对氯离子具有高通透性。相邻细胞通过电耦合,使得细胞中的电活动同步。乙酰胆碱(ACh)和γ-氨基丁酸(GABA)会影响电活动。浴加ACh会增加膜阳离子电导,使细胞去极化,改变锋电位的频率和幅度并引发收缩。浴加GABA会增加氯离子电导,降低锋电位活动并导致超极化和肌肉松弛。蛔虫肌肉袋状区域的突触外ACh受体可被视为烟碱样受体的一个单独亚型。ACh和驱虫激动剂(噻嘧啶、莫仑太尔、左旋咪唑)会使阳离子电导和膜去极化呈剂量依赖性增加,这种增加可被筒箭毒碱、美加明阻断,但不能被六甲铵阻断。除磺酸衍生物外,GABA激动剂的效力与脊椎动物GABAa受体相关。拮抗剂的效力则不然。因此,荷包牡丹碱、一叶萩碱、匹拉唑平、SR95531和RU5135是强效的脊椎动物GABAa拮抗剂,但对GABA受体几乎没有影响。芳基氨基哒嗪GABA拮抗剂在蛔虫GABA受体上的效力顺序:SR95103、SR95132、SR42666、SR95133、SR95531、SR42627和SR42640与在脊椎动物GABAa受体上的效力顺序不同。有人提出该受体可称为GABAn受体。膜片钳研究表明,ACh激活一个非选择性阳离子通道,其主要电导为40 - 50 pS,表观平均开放时间为1.3 ms;还会激活一个电导为20 - 30 pS、开放时间相似的较小通道。噻嘧啶和左旋咪唑也会产生具有相似电导和开放时间的通道开放。(摘要截选至400字)

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