神经递质转运蛋白

神经递质转运蛋白黄芳,费俭,郭礼和（中国科学院上海细胞生物学研究所２０００３１）１神经递质神经递质（Ｎｅｕｒｏｔｒａｎｓｍｉｔｔｅｒ）是指在神经元突触部位传递神经信息的化学物质。递质种类很多,常见的有：乙酸胆碱（Ａｃｈ）,腺嘌呤三磷酸（ＡＴＰ）,氨基...     

脑电超慢涨落图技术在癫痫研究中的应用

目的：观察脑内多种神经递质对癫痫发作的影响。方法：以癫痫患者和ＳＤ大鼠为实验对象,用脑功能检测的最新脑电超电涨落图分析仪（ｅｎｃｅｐｈａｌｏｆｌｕｃｔｕｏｇｒａｍ ｔｅｃｈｎｏｌｏｇｙ,ＥＴ）长时程采集脑电信号,提取在脑电中载有脑神经递质调节系统的震荡信息（即Ｓ谱线）,分析癫痫发作时的脑神经递质的变化。结果：患儿癫痫发作时,Ｓ谱线中Ｓ２（谷氨酸）增高;Ｓ１（γ－氨基丁酸）降低,造成Ｓ１＜Ｓ２。Ｓ５     

腺苷受体拮抗剂对帕金森病小鼠神经递质的影响

运用神经毒剂ＭＰＴＰ（１－ｍｅｔｈｙ－４－ｐｈｅｎｙ－１,２,３,６－ｔｅｔｒａｈｙｄｒｏｐｙｒｉｄｉｎｅ）制作的ＩＣＲ小鼠帕金森病模型,通过荧光测定方法和免疫组织化学方法,测定ＭＰＴＰ及腺甘Ａ２ａ受体拮抗剂喹唑啉（Ｑｕｉｎａｚｏｌｉｎｅ,ＣＰ６６７１３）对单胺类神经递质去甲肾上腺素（ＮＡ）、多巴胺（ＤＡ）、５－羟色胺（５－ＨＴ）及其代谢产物５－羟吲哚乙酸（５－ＨＩＡＡ）和氨基酸类神经递质γ－氨基     

真核生物的信号传导

真核生物的信号传导王钧（中国科学院上海植物生理研究所上海２０００３２）１导官生物的生长发育,对环境的适应都涉及外源（光、温度、气味、盐、各种营养物、毒素、病原激发子、重力、触摸等）和内源（激素、神经递质、细胞因子等等）信号对体内特定部位细胞作用,引起...     

运动性中枢疲劳后脊髓内主要神经递质含量的变化

目的：研究运动性中枢疲劳后脊髓内主要单胺类及氨基酸类神经递质含量的变化,探索运动性疲劳脊髓水平发生机制。方法：运用：Bedford递增负荷运动训练方案建立运动性中枢疲劳模型。将18只雄性成年Wistar大鼠随机分为对照组（C）,训练后即刻组（IT）及训练后3 h恢复组（RT）。用高效液相色谱法（HPLC）检测脊髓内单胺类和氨基酸类神经递质含量的变化。结果：大鼠脊髓内氨基酸类神经递质,在训练后即刻都出现了增高,其中谷氨酸（Glu）、γ-氨基丁酸（GABA）明显增高（P〈0.05）,甘氨酸（Gly）也出现增高但与对照组相比无显著性差异 训练后经3 h恢复后,氨基酸类神经递质含量基本恢复至对照组水平。单胺类神经递质,去甲肾上腺素（NE）,5-羟色胺（5-HT）在训练后即刻则出现降低趋势,且5-羟色胺（5-HT）含量在训练后3 h恢复组出现了明显降低（P〈0.05）。结论：运动性疲劳引起脊髓内神经递质含量的改变,可能与运动性中枢疲劳的发生过程有关。脊髓5-HT在恢复期仍明显降低,提示5-HT可能与疲劳恢复过程有较为密切的关系。     

猕猴体感Ⅰ区皮层内注射新斯的明对皮肤痛阈的影响

猕猴体感Ⅰ区皮层内注射新斯的明对皮肤痛阈的影响黄忠致,韩冠钰（广西医科大学生理学教研室南宁５３００２１）我们曾发现体感Ⅰ区（ＳⅠ区）参与痛觉的调制￣〔１〕。有报道乙酰胆碱（ＡＣｈ）是大脑皮层的神经递质。本研究观察了ＳⅠ区皮层内注射新斯的明使皮层内ＡＣ...     

电磁脉冲对大鼠学习和脑内神经递质的影响

探讨电磁脉冲（ＥＭＰ）对大鼠神经系统的效应。实验采用Ｗｉｓｔａｒ大鼠,ＥＭＰ辐照后不同时间用Ｙ－型迷宫测其学习能力,高效液相色谱法检测脑不同部位的神经递质含量。与假照射组（对照组）相比,照后三天内各测定组大鼠学习能力降低（Ｐ＜０．０５）,其中照射后第１天组的海马内５－羟色胺（５－ＨＴ）和多巴酸（ＤＯＰＡＣ）含量升高（Ｐ＜０．０５）,下丘脑多巴胺（Ｄｏｐａｍｉｎｅ）含量升高（Ｐ＜０．０５）,肾上腺素（Ａｄｒ）含量降低;照后２天组海马Ａｄｒ含量降低（Ｐ＜０．０５）,海马５－ＨＴ含量升高（Ｐ＜０．０５）;照后３天组海马内Ａｄｒ含量降低（Ｐ＜０．０５）。ＥＭＰ能够改变大鼠不同脑区神经递质的含量,降低大鼠学习能力     

通督调神针刺法联合认知功能训练对卒中后认知障碍患者肠道菌群和神经递质的影响

摘要 目的：观察通督调神针刺法联合认知功能训练对卒中后认知障碍患者神经递质、肠道菌群的影响。方法：按照随机数字表法将河北省沧州中西医结合医院2021年7月-2022年10月收治的124例卒中后认知障碍患者分为对照组（62例,认知功能训练）和观察组（62例,认知功能训练、通督调神针刺法联合治疗）。对比两组简易精神状态检查表（MMSE）、日常生活活动（ADL）、蒙特利尔认知评估量表（MoCA）、血清神经递质[去甲肾上腺素（NE）、神经递质乙酰胆碱 （ACh）、5-羟色胺（5-HT）、多巴胺（DA）]、肠道菌群指标。结果：治疗30 d后,观察组MMSE、MoCA、ADL评分高于对照组同期（P<0.05）。治疗30 d后,观察组Ach、DA、NE、5-HT高于对照组同期（P<0.05）。治疗30 d后,观察组大肠埃希菌、肠球菌低于对照组同期,双歧杆菌、乳杆菌高于对照组同期（P<0.05）。结论：卒中后认知障碍患者在认知功能训练基础上结合通督调神针刺法,认知功能、肠道菌群和神经递质水平显著改善,从而有利于改善患者的日常生活活动能力。     

中药天年饮对衰老大鼠脑单胺类神经递质含量的影响

目的：观察中药天年饮（Tiannianyin,TNY-traditional chinese medicine）对D-半乳糖衰老大鼠脑单胺类神经递质去甲肾上腺素（NE）、多巴胺（DA）、5-羟色胺（5-HT）含量的影响。方法：选用成年雄性SD大鼠40只．随机分为4组．每组均为10只：正常组、衰老模型组、TNY用药组、阴性对照组。Ⅱ半乳糖连续腹腔注射制作亚急性衰老的大鼠模型．采用高效液相色谱-电化学法检测各组大鼠下丘脑、海马NE、DA、5-HT的含量。结果：D-半乳糖衰老大鼠下丘脑、海马NE、DA、5-HT的含量明显降低（与正常大鼠相比P〈0．01）：TNY可明显提高脑单胺类神经递质的含量（用药组与模型组相比P〈0．05）。结论：TNY可有效调整中枢神经递质的合成,具有良好延缓衰老的作用。     

小儿先天性巨结肠症酶组织化学变化的研究

小儿先天性巨结肠症（ＨＤ）之病因不甚清楚。国内外学者对其狭窄段各种神经递质的研究较多。而针对细胞能量代谢有关酶类变化研究很少。故本实验对２０例ＨＤ病儿的狭窄段,正常段全层组织进行酶组织化学方法的观察,根据酶反应的强弱分组对比观察。结果发现：（１）ＡＴＰａｓｅ（腺苷三磷酸酶）,ＳＤＨ（琥珀酸脱氢酶）,Ｃｈｅ（胆碱脂酶）,狭窄段酶活性显著高于正常段。（２）ＭＡＯ（单胺氧化酶）活性狭窄段明显低于正常设。（３）狭窄段粘膜下及肌间神经丛,和神经节细胞平均个数明显少于正常段。     

Regulation of nicotinic acetylcholine receptors by protein phosphorylation

Neurotransmitter receptors and ion channels play a critical role in the transduction of signals at chemical synapses. The modulation of neurotransmitter receptor and ion channel function by protein phosphorylation is one of the major regulatory mechanisms in the control of synaptic transmission. The nicotinic acetylcholine receptor (nAcChR) has provided an excellent model system in which to study the modulation of neurotransmitter receptors and ion channels by protein phosphorylation since the structure and function of this receptor have been so extensively characterized. In this article, the structure of the nAcChR from the electric organ of electric fish, skeletal muscle, and the central and peripheral nervous system will be briefly reviewed. Emphasis will be placed on the regulation of the phosphorylation of nAcChR by second messengers and by neurotransmitters and hormones. In addition, recent studies on the functional modulation of nicotinic receptors by protein phosphorylation will be reviewed.     

Structure and function of polycystin channels in primary cilia

Variants in genes which encode for polycystin-1 and polycystin-2 cause most forms of autosomal dominant polycystic disease (ADPKD). Despite our strong understanding of the genetic determinants of ADPKD, we do not understand the structural features which govern the function of polycystins at the molecular level, nor do we understand the impact of most disease-causing variants on the conformational state of these proteins. These questions have remained elusive because polycystins localize to several organelle membranes, including the primary cilia. Primary cilia are microtubule based organelles which function as cellular antennae. Polycystin-2 and related polycystin-2 L1 are members of the transient receptor potential (TRP) ion channel family, and form distinct ion channels in the primary cilia of disparate cell types which can be directly measured. Polycystin-1 has both ion channel and adhesion G-protein coupled receptor (GPCR) features—but its role in forming a channel complex or as a channel subunit chaperone is undetermined. Nonetheless, recent polycystin structural determination by cryo-EM has provided a molecular template to understand their biophysical regulation and the impact of disease-causing variants. We will review these advances and discuss hypotheses regarding the regulation of polycystin channel opening by their structural domains within the context of the primary cilia.     

Analysis of the action of lidocaine on insect sodium channels

A new class of sodium channel blocker insecticides (SCBIs), which include indoxacarb, its active metabolite, DCJW, and metaflumizone, preferably block inactivated states of both insect and mammalian sodium channels in a manner similar to that by which local anesthetic (LA) drugs block mammalian sodium channels. A recent study showed that two residues in the cockroach sodium channel, F1817 and Y1824, corresponding to two key LA-interacting residues identified in mammalian sodium channels are not important for the action of SCBIs on insect sodium channels, suggesting unique interactions of SCBIs with insect sodium channels. However, the mechanism of action of LAs on insect sodium channels has not been investigated. In this study, we examined the effects of lidocaine on a cockroach sodium channel variant, BgNa(v)1-1a, and determined whether F1817 and Y1824 are also critical for the action of LAs on insect sodium channels. Lidocaine blocked BgNa(v)1-1a channels in the resting state with potency similar to that observed in mammalian sodium channels. Lidocaine also stabilized both fast-inactivated and slow-inactivated states of BgNa(v)1-1a channels, and caused a limited degree of use- and frequency-dependent block, major characteristics of LA action on mammalian sodium channels. Alanine substitutions of F1817 and Y1824 reduced the sensitivity of the BgNa(v)1-1a channel to the use-dependent block by lidocaine, but not to tonic blocking and inactivation stabilizing effects of lidocaine. Thus, similar to those on mammalian sodium channels, F1817 and Y1824 are important for the action of lidocaine on cockroach sodium channels. Our results suggest that the receptor sites for lidocaine and SCBIs are different on insect sodium channels.     

昆虫钠离子通道基因突变及其与杀虫剂抗性关系的研究进展

昆虫电压门控钠离子通道(voltage-gated sodium channel)存在于所有可兴奋细胞的细胞膜上,在动作电位的产生和传导上起重要作用,是有机氯和拟除虫菊酯杀虫剂的靶标位点。在农业和医学害虫控制过程中,由于有机氯和拟除虫菊酯杀虫剂的广泛使用,抗药性问题日益突出。其中,由于钠离子通道基因突变,降低了钠离子通道对有机氯和拟除虫菊酯类杀虫剂的亲和性,从而产生击倒抗性(knock-down resistance, kdr),已成为抗性产生的重要机制之一。本文综述了昆虫钠离子通道的跨膜拓扑结构、功能、进化及其基因的克隆;更重要的是总结了已报道的40多种昆虫40个钠离子通道基因非同义突变,以及钠离子通道基因选择性mRNA剪接和编辑,以及它们与杀虫剂抗性的关系;也评述了钠离子通道基因突变引起蛋白质结构的改变,从而对杀虫剂抗性的影响机制。这些研究对于进一步鉴定与杀虫剂抗性相关的突变及抗性机制,开发有机氯和拟除虫菊酯类杀虫剂抗性分子监测方法具有重要意义。     

Molecular dissection of Cl--selective Cys-loop receptor points to components that are dispensable or essential for channel activity

Cys-loop receptors are pentameric ligand-gated ion channels (pLGICs) that bind neurotransmitters to open an intrinsic transmembrane ion channel pore. The recent crystal structure of a prokaryotic pLGIC from the cyanobacterium Gloeobacter violaceus (GLIC) revealed that it naturally lacks an N-terminal extracellular α helix and an intracellular domain that are typical of eukaryotic pLGICs. GLIC does not respond to neurotransmitters acting at eukaryotic pLGICs but is activated by protons. To determine whether the structural differences account for functional differences, we used a eukaryotic chimeric acetylcholine-glutamate pLGIC that was modified to carry deletions corresponding to the sequences missing in the prokaryotic homolog GLIC. Deletions made in the N-terminal extracellular α helix did not prevent the expression of receptor subunits and the appearance of receptor assemblies on the cell surface but abolished the capability of the receptor to bind α-bungarotoxin (a competitive antagonist) and to respond to the neurotransmitter. Other truncated chimeric receptors that lacked the intracellular domain did bind ligands; displayed robust acetylcholine-elicited responses; and shared with the full-length chimeric receptor similar anionic selectivity, effective open pore diameter, and unitary conductance. We suggest that the integrity of the N-terminal α helix is crucial for ligand accommodation because it stabilizes the intersubunit interfaces adjacent to the neurotransmitter-binding pocket(s). We also conclude that the intracellular domain of the chimeric acetylcholine-glutamate receptor does not modulate the ion channel conductance and is not involved in positioning of the pore-lining helices in the conformation necessary for coordinating a Cl- ion within the intracellular vestibule of the ion channel pore.     

Synaptic Neurotransmitter-Gated Receptors

Since the discovery of the major excitatory and inhibitory neurotransmitters and their receptors in the brain, many have deliberated over their likely structures and how these may relate to function. This was initially satisfied by the determination of the first amino acid sequences of the Cys-loop receptors that recognized acetylcholine, serotonin, GABA, and glycine, followed later by similar determinations for the glutamate receptors, comprising non-NMDA and NMDA subtypes. The last decade has seen a rapid advance resulting in the first structures of Cys-loop receptors, related bacterial and molluscan homologs, and glutamate receptors, determined down to atomic resolution. This now provides a basis for determining not just the complete structures of these important receptor classes, but also for understanding how various domains and residues interact during agonist binding, receptor activation, and channel opening, including allosteric modulation. This article reviews our current understanding of these mechanisms for the Cys-loop and glutamate receptor families.To understand how neurons communicate with each other requires a fundamental understanding of neurotransmitter receptor structure and function. Neurotransmitter-gated ion channels, also known as ionotropic receptors, are responsible for fast synaptic transmission. They decode chemical signals into electrical responses, thereby transmitting information from one neuron to another. Their suitability for this important task relies on their ability to respond very rapidly to the transient release of neurotransmitter to affect cell excitability.In the central nervous system (CNS), fast synaptic transmission results in two main effects: neuronal excitation and inhibition. For excitation, the principal neurotransmitter involved is glutamate, which interacts with ionotropic (integral ion channel) and metabotropic (second-messenger signaling) receptors. The ionotropic glutamate receptors are permeable to cations, which directly cause excitation. Acetylcholine and serotonin can also activate specific cation-selective ionotropic receptors to affect neuronal excitation. For controlling cell excitability, inhibition is important, and this is mediated by the neurotransmitters GABA and glycine, causing an increased flux of anions. GABA predominates as the major inhibitory transmitter throughout the CNS, whereas glycine is of greater importance in the spinal cord and brainstem. They both activate specific receptors—for GABA, there are ionotropic and metabotropic receptors, whereas for glycine, only ionotropic receptors are known to date.Together with acetylcholine- and serotonin-gated channels, GABA and glycine ionotropic receptors form the superfamily of Cys-loop receptors, which differs in many aspects from the superfamily of ionotropic glutamate receptors. Over the last two decades, our knowledge of the structure and function of ionotropic receptors has grown rapidly. In this article, we summarize our current understanding of the molecular operation of these receptors and how we can now begin to interpret the role of receptor structure in agonist binding, channel activation, and allosteric modulation of Cys-loop and glutamate receptor families. Further details on the regulation and trafficking of neurotransmitter receptors in synaptic structure and plasticity can be found in accompanying articles.     

Insect sodium channels and insecticide resistance

Voltage-gated sodium channels are essential for the generation and propagation of action potentials (i.e., electrical impulses) in excitable cells. Although most of our knowledge about sodium channels is derived from decades of studies of mammalian isoforms, research on insect sodium channels is revealing both common and unique aspects of sodium channel biology. In particular, our understanding of the molecular dynamics and pharmacology of insect sodium channels has advanced greatly in recent years, thanks to successful functional expression of insect sodium channels in Xenopus oocytes and intensive efforts to elucidate the molecular basis of insect resistance to insecticides that target sodium channels. In this review, I discuss recent literature on insect sodium channels with emphases on the prominent role of alternative splicing and RNA editing in the generation of functionally diverse sodium channels in insects and the current understanding of the interactions between insect sodium channels and insecticides.     

双孔钾通道TREK-1结构、分布、调控因素及其抗癫痫作用的研究进展

钾离子通道是最大最复杂的离子通道家族,迄今为止在人类基因组中共克隆出了70余种钾离子通道亚型,其中双孔钾离子通道是近年来新发现的一类钾离子通道亚家族,它们在结构上与电压依赖性钾通道、钙激活钾通道,内向整流型钾通道等传统的单孔钾离子通道差异很大。双孔钾离子通道,具有4个跨膜片段,形成独特的2个孔道结构域,主要介导背景钾电流。由于其介导背景钾电流而参与并维持静息膜电位形成等重要生理作用而备受关注。近年来研究最多的双孔钾通道TREK-1几乎表达于机体的每一个细胞,可被细胞内酸度、膜牵张、多不饱和脂肪酸、温度、受体偶联第二信使系统调控,调节细胞兴奋性,参与一系列生理、病理过程,与神经系统疾病如癫痫密切相关,本文就此做一综述。     

Voltage-dependent potassium channels: minK and Shaker families

In the last 4 years, the molecular identity of several types of voltage-dependent potassium channels has been discovered. These include channels that terminate action potentials and control repetitive neuronal firing, as well as channels whose biological role is not yet understood. The majority of these are encoded by genes related to the Drosophila Shaker gene. The large number of genes comprising the Shaker gene family, coupled with the existence of different channels that result from alternatively spliced messages from the same gene, provide both vertebrates and invertebrates with a wide selection of channels whose voltage-dependence and kinetics can be tailored to the needs of a specific cell. Mutagenesis experiments on such channels are providing new information on those regions of the protein that govern essential aspects of channel activity, such as gating by voltage and ion permeation. Another gene, unrelated to the Shaker family, encodes a voltage-dependent potassium channel that activates much more slowly than the Shaker channels. This has been termed the MinK channel.