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首页> 外文学位 >Regulation of intracellular free calcium by cholinergic receptors on chick ciliary ganglion neurons.
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Regulation of intracellular free calcium by cholinergic receptors on chick ciliary ganglion neurons.

机译：胆碱能受体对鸡睫状神经节神经元的细胞内游离钙的调节。

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摘要

Neurons are specialized in their multiple uses of calcium as a signalling molecule as well as in their many mechanisms that regulate the influx and removal of calcium from the cytoplasm. In this work, I have focused on neurons of the chick ciliary ganglion, where a single neurotransmitter, acetylcholine (ACh), can stimulate as many as three classes of cholinergic receptors: two with nicotinic pharmacology (one synaptic and the other extrasynaptic) and one with muscarinic pharmacology.; All three classes of acetylcholine receptors (AChRs) elevate intracellular free calcium ( (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar}) as measured using the calcium indicator, fluo-3. The synaptic-type nicotinic AChRs are highly permeable to calcium, as demonstrated using constant field analysis, and are more like other neuronal AChRs in this respect than like synaptic AChRs on muscle. Moreover, the receptors are as effective at elevating (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} in the neurons under physiological conditions as are the more abundant {dollar}alpha{dollar}Bgt-AChRs, indicating that the same neurons can express and maintain at least two classes of nicotinic receptors with this feature. Both classes of nicotinic AChRs rely heavily on activation of voltage-dependent calcium channels (VDCCs) for global elevation of cytoplasmic calcium. When the membrane potential is held near rest, however, the synaptic-type AChRs can promote substantial calcium influx without contributions from VDCCs. As a result, the receptors could, in principle, regulate calcium-dependent events without cell depolarization being a prerequisite. Calcium flux through nicotinic AChRs may have greatest impact on calcium levels in microdomains near the plasma membrane. In this case, the two classes of receptors could induce wholly different sets of calcium-dependent events by virtue of the different distributions the receptor subtypes have in the membrane.; Muscarinic receptors stimulate the production of inositol phosphates and evoke an oscillatory pattern of (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} elevation. This oscillatory pattern of (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} response is not seen upon nicotine stimulation. Also unlike the nicotinic AChRs, muscarinic receptors mobilize both intracellular and extracellular calcium sources. The endogenous ligand, acetylcholine, can induce oscillatory or non-oscillatory patterns of (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} elevation, depending upon the concentration of agonist used. The pattern depends on the combination of receptors activated. Muscarinic receptors are activated at low concentrations of ACh and induce an oscillatory (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} elevation. Both nicotinic and muscarinic receptors are active at higher ACh concentrations, together inducing a sustained (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} elevation. Each of the temporal patterns of (Ca{dollar}sp{lcub}2+{rcub}rbracksb{lcub}rm i{rcub}{dollar} elevation may engage a unique set of calcium-dependent cellular processes, including, for example, exocytosis, cytoskeletal restructuring, gene expression, or cell death.
机译：神经元擅长于将钙作为信号分子的多种用途，以及调节钙从细胞质中流入和清除的多种机制。在这项工作中，我集中研究了鸡睫状神经节的神经元，其中单个神经递质乙酰胆碱（ACh）可以刺激多达三类胆碱能受体：两种具有烟碱药理作用（一种是突触的，另一种是突触的）。具有毒蕈碱药理学。所有三类乙酰胆碱受体（AChR）都会升高钙离子指示剂Fluo-所测得的细胞内游离钙（（Ca {dollar} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}） 3.如通过恒定场分析所证实，突触型烟碱型AChRs对钙具有很高的渗透性，并且在这方面更像其他神经元AChRs，而不是肌肉上的突触型AChRs。此外，受体在提升（Ca {在生理条件下神经元中的美元} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}以及更丰富的{dolal} alpha {dollar} Bgt-AChRs，表明相同的神经元可以表达并维持至少两类烟碱样受体，这两种烟碱型AChR都严重依赖于电压依赖性钙通道（VDCC）的激活，从而使细胞质钙整体升高，但是当膜电位保持在接近静止状态时， ，突触型AChRs可以促进没有VDCC贡献的Cium流入。结果，原则上受体可以调节钙依赖性事件，而无需细胞去极化。通过烟碱型AChR的钙通量可能对质膜附近微区的钙水平有最大影响。在这种情况下，由于受体亚型在膜中的分布不同，这两类受体可以诱导完全不同的钙依赖性事件。毒蕈碱受体刺激肌醇磷酸酯的产生，并引起（Ca {dollar} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}升高的振荡模式。（Ca {dollar尼古丁刺激后未见} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}反应。与烟碱型AChRs不同，毒蕈碱受体可动员细胞内和细胞外钙源。乙酰胆碱可以诱导（Ca {dollar} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}升高的振荡或非振荡模式，具体取决于所用激动剂的浓度。毒蕈碱受体在低浓度的ACh中被激活，并引起振荡（Ca {dollar} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}升高。两种烟碱和毒蕈碱受体在较高的ACh浓度下具有活性，共同诱导持续性（Ca {dollar} sp {lcub} 2+ {r {cub} rbracksb {lcub} rm i {rcub} {dollar}高程。 （Ca {dollar} sp {lcub} 2+ {rcub} rbracksb {lcub} rm i {rcub} {dollar}升高的每个时间模式都可能涉及一组独特的钙依赖性细胞过程，包括例如胞吐，细胞骨架重组，基因表达或细胞死亡。

著录项

  • 作者

    Rathouz, Margaret M.;

  • 作者单位

    University of California, San Diego.;

  • 授予单位 University of California, San Diego.;
  • 学科 Biology General.; Biology Neuroscience.; Biology Cell.
  • 学位 Ph.D.
  • 年度 1995
  • 页码 119 p.
  • 总页数 119
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;神经科学;细胞生物学;
  • 关键词

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