• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

缝隙连接通道和 P2X3 受体的功能偶联有助于神经病理性疼痛处理。

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing.

机构信息

Institut für Pharmakologie und Klinische Pharmazie, Goethe-Universität Frankfurt am Main, 60438 Frankfurt am Main, Hessen, Germany.

Pharmakologie, Toxikologie und Klinische Pharmazie, Institut für Pharmazie, Universität Tübingen, 72076 Tübingen, Baden-Württemberg, Germany.

出版信息

Int J Mol Sci. 2021 Jan 2;22(1):405. doi: 10.3390/ijms22010405.

DOI:10.3390/ijms22010405
PMID:33401689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7795269/
Abstract

The sodium-activated potassium channel Slack (K1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.

摘要

钠激活钾通道 Slack（K1.1、Slo2.2 或 Kcnt1）在感觉神经元群体中高度表达，在其中介导钠激活钾电流（I）并调节神经元活性。先前的研究表明 Slack 参与了神经性疼痛的处理。然而，这种情况下 Slack 活性调节的机制尚不清楚。使用全细胞膜片钳记录，我们发现外周神经损伤后，小鼠感觉神经元中的 Slack 介导的 I 减少，从而导致神经性疼痛过敏。有趣的是，在感觉神经元的一个群体中，Slack 与 ATP 敏感的 P2X3 受体密切相关。体外实验表明，Slack 介导的 I 可能会对 P2X3 激活产生双向调节。此外，缺乏 Slack 的小鼠对 P2X3 刺激的伤害性反应发生改变。我们的研究确定了 P2X3/Slack 信号作为外周神经损伤后敏感性增加的一种机制，并提出了一种治疗神经性疼痛的潜在新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/6e01fe74ea31/ijms-22-00405-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/570a7e826f55/ijms-22-00405-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/09895a7dc5f0/ijms-22-00405-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/9a0b269e09de/ijms-22-00405-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/95a5d95b3545/ijms-22-00405-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/9d0ca5d7d1fb/ijms-22-00405-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/cef4193bfff6/ijms-22-00405-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/c94df7b95f90/ijms-22-00405-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/6e01fe74ea31/ijms-22-00405-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/570a7e826f55/ijms-22-00405-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/09895a7dc5f0/ijms-22-00405-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/9a0b269e09de/ijms-22-00405-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/95a5d95b3545/ijms-22-00405-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/9d0ca5d7d1fb/ijms-22-00405-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/cef4193bfff6/ijms-22-00405-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/c94df7b95f90/ijms-22-00405-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ba9/7795269/6e01fe74ea31/ijms-22-00405-g008.jpg

相似文献

1
Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing.缝隙连接通道和 P2X3 受体的功能偶联有助于神经病理性疼痛处理。
Int J Mol Sci. 2021 Jan 2;22(1):405. doi: 10.3390/ijms22010405.
2
Slack channels expressed in sensory neurons control neuropathic pain in mice.感觉神经元中表达的松弛素通道控制小鼠的神经性疼痛。
J Neurosci. 2015 Jan 21;35(3):1125-35. doi: 10.1523/JNEUROSCI.2423-14.2015.
3
Slack Potassium Channels Modulate TRPA1-Mediated Nociception in Sensory Neurons.松弛钾通道调节感觉神经元中TRPA1介导的伤害感受。
Cells. 2022 May 19;11(10):1693. doi: 10.3390/cells11101693.
4
GPR151 in nociceptors modulates neuropathic pain via regulating P2X3 function and microglial activation.伤害感受器中的 GPR151 通过调节 P2X3 功能和小胶质细胞激活来调节神经性疼痛。
Brain. 2021 Dec 16;144(11):3405-3420. doi: 10.1093/brain/awab245.
5
Control of P2X3 channel function by metabotropic P2Y2 utp receptors in primary sensory neurons.初级感觉神经元中代谢型 P2Y2 UTP 受体对 P2X3 通道功能的控制。
Mol Pharmacol. 2013 Mar;83(3):640-7. doi: 10.1124/mol.112.082099. Epub 2012 Dec 18.
6
The scaffold protein calcium/calmodulin-dependent serine protein kinase controls ATP release in sensory ganglia upon P2X3 receptor activation and is part of an ATP keeper complex.支架蛋白钙/钙调蛋白依赖性丝氨酸蛋白激酶在P2X3受体激活后控制感觉神经节中的ATP释放，并且是ATP维持复合物的一部分。
J Neurochem. 2016 Aug;138(4):587-97. doi: 10.1111/jnc.13680. Epub 2016 Jun 18.
7
The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).抗精神病药物洛沙平是一种钠激活钾通道松弛（Slo2.2）的开放剂。
J Pharmacol Exp Ther. 2012 Mar;340(3):706-15. doi: 10.1124/jpet.111.184622. Epub 2011 Dec 13.
8
A317491 relieved HIV gp120-associated neuropathic pain involved in P2X receptor in dorsal root ganglia.A317491缓解了与背根神经节中P2X受体相关的HIV gp120介导的神经性疼痛。
Brain Res Bull. 2017 Apr;130:81-89. doi: 10.1016/j.brainresbull.2017.01.002. Epub 2017 Jan 5.
9
Protein kinase A-induced internalization of Slack channels from the neuronal membrane occurs by adaptor protein-2/clathrin-mediated endocytosis.蛋白激酶A诱导的Slack通道从神经元膜内化是通过衔接蛋白2/网格蛋白介导的内吞作用发生的。
J Biol Chem. 2017 Nov 24;292(47):19304-19314. doi: 10.1074/jbc.M117.804716. Epub 2017 Oct 5.
10
Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain.A/J近交系小鼠中P2X3受体依赖性感觉功能的下调
Eur J Neurosci. 2002 May;15(9):1444-50. doi: 10.1046/j.1460-9568.2002.01982.x.

引用本文的文献

1
Redox-dependent activation of protein kinase G1α contributes to transient receptor potential cation channel subfamily V member 1-mediated acute nociceptive pain behavior.蛋白激酶G1α的氧化还原依赖性激活促成瞬时受体电位阳离子通道亚家族V成员1介导的急性伤害性疼痛行为。
Redox Rep. 2025 Dec;30(1):1-17. doi: 10.1080/13510002.2025.2549954. Epub 2025 Aug 25.
2
Advanced cancer perineural invasion induces profound peripheral neuronal plasticity, pain, and somatosensory mechanical deactivation, unmitigated by the lack of TNFR1. Part 2. Biophysics and gene expression.晚期癌症神经周围浸润会引发严重的外周神经元可塑性、疼痛和体感机械失活，且不会因缺乏肿瘤坏死因子受体1（TNFR1）而减轻。第2部分。生物物理学与基因表达。
Mol Pain. 2025 Jan-Dec;21:17448069251323666. doi: 10.1177/17448069251323666. Epub 2025 Feb 13.
3

本文引用的文献

1
P2X3-Containing Receptors as Targets for the Treatment of Chronic Pain.P2X3 受体在慢性疼痛治疗中的作用靶点。
Neurotherapeutics. 2020 Jul;17(3):826-838. doi: 10.1007/s13311-020-00934-2. Epub 2020 Oct 2.
2
Von Frey testing revisited: Provision of an online algorithm for improved accuracy of 50% thresholds.福里厄测试再探：提供在线算法以提高 50%阈值的准确性。
Eur J Pain. 2020 Apr;24(4):783-790. doi: 10.1002/ejp.1528. Epub 2020 Jan 23.
3
Loxapine for Treatment of Patients With Refractory, Chemotherapy-Induced Neuropathic Pain: A Prematurely Terminated Pilot Study Showing Efficacy But Limited Tolerability.
Slick potassium channels limit TRPM3-mediated activation of sensory neurons.光滑钾通道限制TRPM3介导的感觉神经元激活。
Front Pharmacol. 2024 Dec 18;15:1459735. doi: 10.3389/fphar.2024.1459735. eCollection 2024.
4
Discovery of a Small Molecule Activator of Slack (Kcnt1) Potassium Channels That Significantly Reduces Scratching in Mouse Models of Histamine-Independent and Chronic Itch.发现一种小分子 Slack（Kcnt1）钾通道激活剂，可显著减少组胺非依赖性和慢性瘙痒模型中小鼠的搔抓。
Adv Sci (Weinh). 2024 Apr;11(15):e2307237. doi: 10.1002/advs.202307237. Epub 2024 Feb 13.
5
The Contribution of TRPA1 to Corneal Thermosensitivity and Blink Regulation in Young and Aged Mice.TRPA1 对年轻和老年小鼠角膜热敏性和眨眼调节的贡献。
Int J Mol Sci. 2023 Aug 9;24(16):12620. doi: 10.3390/ijms241612620.
6
Colorectal Cancer and Purinergic Signalling: An Overview.结直肠癌与嘌呤能信号传导：综述
Cancers (Basel). 2022 Oct 6;14(19):4887. doi: 10.3390/cancers14194887.
7
Slack Potassium Channels Modulate TRPA1-Mediated Nociception in Sensory Neurons.松弛钾通道调节感觉神经元中TRPA1介导的伤害感受。
Cells. 2022 May 19;11(10):1693. doi: 10.3390/cells11101693.
8
The Slack Channel Deletion Causes Mechanical Pain Hypersensitivity in Mice.松弛通道缺失导致小鼠机械性疼痛超敏反应。
Front Mol Neurosci. 2022 Mar 11;15:811441. doi: 10.3389/fnmol.2022.811441. eCollection 2022.
洛沙平治疗难治性化疗诱导的神经性疼痛患者：一项提前终止的初步研究显示有效但耐受性有限。
Front Pharmacol. 2019 Jul 25;10:838. doi: 10.3389/fphar.2019.00838. eCollection 2019.
4
Narciclasine exerts anti-inflammatory actions by blocking leukocyte-endothelial cell interactions and down-regulation of the endothelial TNF receptor 1.纳曲昔林通过阻断白细胞-内皮细胞相互作用和下调内皮细胞 TNF 受体 1 发挥抗炎作用。
FASEB J. 2019 Aug;33(8):8771-8781. doi: 10.1096/fj.201802440R. Epub 2019 Apr 24.
5
Action of MK-7264 (gefapixant) at human P2X3 and P2X2/3 receptors and in vivo efficacy in models of sensitisation.MK-7264（gefapixant）在人 P2X3 和 P2X2/3 受体上的作用及其在致敏模型中的体内疗效。
Br J Pharmacol. 2019 Jul;176(13):2279-2291. doi: 10.1111/bph.14677. Epub 2019 May 11.
6
Magi-1 scaffolds Na1.8 and Slack K channels in dorsal root ganglion neurons regulating excitability and pain.Magi-1 支架在背根神经节神经元中调节兴奋性和疼痛的 Na1.8 和 Slack K 通道。
FASEB J. 2019 Jun;33(6):7315-7330. doi: 10.1096/fj.201802454RR. Epub 2019 Mar 12.
7
P2X3 receptors are transducers of sensory signals.P2X3 受体是感觉信号的传感器。
Brain Res Bull. 2019 Sep;151:119-124. doi: 10.1016/j.brainresbull.2018.12.020. Epub 2019 Jan 17.
8
Distinct functions of soluble guanylyl cyclase isoforms NO-GC1 and NO-GC2 in inflammatory and neuropathic pain processing.NO-GC1 和 NO-GC2 可溶性鸟苷酸环化酶同工型在炎症性和神经性疼痛处理中的不同功能。
Pain. 2019 Mar;160(3):607-618. doi: 10.1097/j.pain.0000000000001440.
9
Author Correction: The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand-gated cationic channel.作者更正：ASIC3/P2X3同源受体是一种与疼痛相关的配体门控阳离子通道。
Nat Commun. 2018 Aug 17;9(1):3351. doi: 10.1038/s41467-018-05621-7.
10
Molecular Architecture of the Mouse Nervous System.小鼠神经系统的分子结构。
Cell. 2018 Aug 9;174(4):999-1014.e22. doi: 10.1016/j.cell.2018.06.021.