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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 总被引:1,自引:0,他引:1
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。 相似文献
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电压门控型钠离子通道(Voltage-gated sodium channel,VGSC)广泛分布于兴奋性细胞,是电信号扩大和传导的主要介质,在神经细胞以及心肌细胞兴奋传导等方面发挥重要作用。钠离子通道结构和功能的异常会改变细胞的兴奋性,从而导致多种疾病的发生,如神经性疼痛、癫痫,以及心律失常等。目前临床上多采用钠离子通道抑制剂治疗上述疾病。近些年,研究人员陆续从动物的毒液中分离纯化出具有调控钠离子通道功能的神经毒素。这些神经毒素多为化合物或小分子多肽。现已有医药研发公司将这些天然的神经毒素进行定向设计改造成钠离子通道靶向药物用于临床疾病的治疗。此外,来源于七鳃鳗Lampetra japonica口腔腺的富含半胱氨酸分泌蛋白(Cysteine-rich buccal gland protein,CRBGP)也首次被证明能够抑制海马神经元和背根神经元的钠离子电流。以下针对钠离子通道疾病及其抑制剂生物学功能的最新研究进展进行分析归纳。 相似文献
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疼痛是一种与组织损伤或潜在的损伤相关的不愉快的主观感觉和情感体验,是机体受到伤害性刺激后产生的一种防御反应。伤害性感觉神经元细胞膜上的电压门控钠离子通道是细胞表面一类跨膜糖蛋白,负责可兴奋细胞动作电位的产生和传导,并且在炎性痛、神经病理性疼痛和功能性痛的产生、传导以及维持上起到了重要的作用,成为近年来疼痛病理生理机制研究和疼痛治疗的分子靶标。本文将就痛觉相关钠离子通道的类型,结构,及其表达和功能的改变与疼痛的关系进行综述。 相似文献
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电压门控钠离子通道疾病的研究进展 总被引:1,自引:0,他引:1
细胞膜上的电压门控钠离子通道(Voltage-gated Sodium Channels,VGSCs)是细胞形成动作电位过程中重要的组成构件,由一个大的α亚基和一个或多个不同的β亚基组成,中央是具高度选择性只允许钠离子通过的亲水通道。电压门控钠离子通道在调节细胞膜电位、维持细胞离子稳态、细胞增殖和凋亡等生理过程中发挥着重要作用,因而钠离子通道自身的异变或是相关基因的变异都可能引起一系列身体病变。本文主要介绍了电压门控钠离子通道的结构与功能,阐述了其与癌细胞侵袭转移和神经病理性疼痛的关系,并介绍了几种典型的由钠离子通道基因变异引起的疾病。随着对电压门控钠离子通道及其异常分子机制研究的不断深入,新成果将为生理学、药理学和病理学等领域的研究提供理论基础和新的研究思路,为离子通道疾病的临床预防、诊断与治疗找到新途径。 相似文献
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昆虫生长调节剂的研究进展 总被引:22,自引:2,他引:20
昆虫生长调节剂(Insectgrowthregulator)是一类影响昆虫正常生长和发育的化学物质,由于它对昆虫生长发育中生理过程的破坏而使昆虫死亡。按其作用方式主要分为苯申酰基本基豚类、保幼激素类似物和抗保幼激素类等。这些称为第三代的杀虫药剂,由于具有和常规杀虫剂不同的独特作用方式而越来越引起人们的兴趣。它们具有选择毒性,只对昆虫有效,对人畜比较安全,因而有很大的发展前途。但就其应用价值来说,苯甲酸基苯基胸类更有实际应用意义。本文仅就近年来苯甲酸基苯基际类及其它新出现的一些昆虫生长调节剂的一研究进展简述如下。!李… 相似文献
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光驱动钠离子泵是近年来发现的全新的光遗传学工具蛋白,在光激发下向膜外主动运输钠离子。然而,其钠离子传递的机制仍不清楚。该家族成员NdR2的可见吸收光谱、荧光光谱和等温滴定量热的结果说明:基态下的NdR2不结合钠离子。进一步的钠离子传递动力学和功能实验发现NdR2在酸性条件下的钠离子传递发生改变。这种pH依赖性的钠离子传递有助于深入理解光驱动钠离子泵中的钠离子的传递机制。 相似文献
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钠通道NaV1.7是电压门控性钠通道的亚型之一。大多数钠离子通道NaV1.7表达在背根神经节(DRG)小C纤维的伤害性感受器上,具有缓慢开放和缓慢关闭失活的特点。它能够产生大量的斜坡电流,降低感觉神经元中动作电位产生的阈值,放大外来小的缓慢的去极化斜坡电流,从而增加神经元兴奋性,对疼痛的产生、传递、调节具有关键性作用。随着遗传学研究的不断深入,钠离子通道NaV1.7的功能获得性突变和功能缺失性突变,使其成为了新型镇痛疗法中一个的特别有吸引力的药物靶点,受到人们的广泛关注。而研究发现,NaV1.7通道在不同因素引起的神经病理性疼痛中通过不同途径提高神经元兴奋性,参与神经病理性疼痛,给NaV1.7选择性抑制剂研发带来了巨大阻碍。目前,虽然已有的NaV1.7选择性抑制剂具备有效镇痛作用,且无明显副作用或成瘾问题,但寻找NaV1.7选择性配体极其困难。此外,现有的NaV1.7选择性抑制剂也因神经病理性疼痛类型的不同在抑制效力、靶向性、安全性以及可行性等方面存在差异。提示寻找NaV1.7通道作用于不同神经病理性疼痛的普遍机制或NaV1.7通道特有的受体结合位点,可能是未来NaV1.7选择性抑制剂研发的主要方向。本文就NaV1.7通道在不同因素引起的神经病理性疼痛中的主要作用进行简要综述。 相似文献
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Intensive pyrethroid use in insect control has led to resistance buildup among various pests. One alternative to battle this problem envisions the combined use of synergistically acting insecticidal compounds. Pyrethroids, scorpion - and β-toxins, and brevetoxins bind to distinct receptor sites on voltage-gated sodium channels (NaChs) and modify their function. The binding affinity of scorpion -toxins to locust, but not rat-brain NaChs, is allosterically increased by pyrethroids and by brevetoxin-1. Brevetoxin-1 also increases the binding of an excitatory β-toxin to insect NaChs. These results reveal differences between insect and mammalian NaChs and may be exploited in new strategies of insect control. 相似文献
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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. 相似文献
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Tassa Saldi Kent Riemondy Benjamin Erickson David L. Bentley 《Molecular cell》2021,81(8):1789-1801.e5
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A long isoform of the human Epithelial Sodium Channel (ENaC) α subunit has been identified, but little data exist regarding the properties or regulation of channels formed by α728. The baseline whole cell conductance of oocytes expressing trimeric α728βγ channels was 898.1 ± 277.2 and 49.59 ± 13.2 µS in low and high sodium solutions, respectively, and was 11 and 2 fold higher than the conductances of α669βγ in same solutions. α728βγ channels were also 2 to 5 fold less sensitive to activation by the serine proteases subtilisin and trypsin than α669βγ in low and high Na+ conditions. The long isoform exhibited lower levels of full length and cleaved protein at the plasma membrane and a rightward shifted sensitivity to inhibition by increases of [Na+]i. Both channels displayed similar single channel conductances of 4 pS, and both were activated to a similar extent by reducing temperature, altogether indicating that activation of baseline conductance of α728βγ was likely mediated by enhanced channel activity or open probability. Expression of α728 in native kidneys was validated in human urinary exosomes. These data demonstrate that the long isoform of αENaC forms the structural basis of a channel with different activity and regulation, which may not be easily distinguishable in native tissue, but may underlie sodium hyperabsorption and salt sensitive differences in humans. 相似文献
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《Channels (Austin, Tex.)》2013,7(1):30-43
A long isoform of the human Epithelial Sodium Channel (ENaC) α subunit has been identified, but little data exist regarding the properties or regulation of channels formed by α728. The baseline whole cell conductance of oocytes expressing trimeric α728βγ channels was 898.1 ± 277.2 and 49.59 ± 13.2 µS in low and high sodium solutions, respectively, and was 11 and 2 fold higher than the conductances of α669βγ in same solutions. α728βγ channels were also 2 to 5 fold less sensitive to activation by the serine proteases subtilisin and trypsin than α669βγ in low and high Na+ conditions. The long isoform exhibited lower levels of full length and cleaved protein at the plasma membrane and a rightward shifted sensitivity to inhibition by increases of [Na+]i. Both channels displayed similar single channel conductances of 4 pS, and both were activated to a similar extent by reducing temperature, altogether indicating that activation of baseline conductance of α728βγ was likely mediated by enhanced channel activity or open probability. Expression of α728 in native kidneys was validated in human urinary exosomes. These data demonstrate that the long isoform of αENaC forms the structural basis of a channel with different activity and regulation, which may not be easily distinguishable in native tissue, but may underlie sodium hyperabsorption and salt sensitive differences in humans. 相似文献