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从鱿鱼巨轴突到自动膜片钳:毒液与抗蛇毒血清研究中的电生理学

From squid giant axon to automated patch-clamp: electrophysiology in venom and antivenom research.

作者信息

Ahmadi Shirin, Benard-Valle Melisa, Boddum Kim, Cardoso Fernanda C, King Glenn F, Laustsen Andreas Hougaard, Ljungars Anne

机构信息

Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.

Sophion Bioscience, Ballerup, Denmark.

出版信息

Front Pharmacol. 2023 Aug 24;14:1249336. doi: 10.3389/fphar.2023.1249336. eCollection 2023.

DOI:10.3389/fphar.2023.1249336
PMID:37693897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10484000/
Abstract

Ion channels play a crucial role in diverse physiological processes, including neurotransmission and muscle contraction. Venomous creatures exploit the vital function of ion channels by producing toxins in their venoms that specifically target these ion channels to facilitate prey capture upon a bite or a sting. Envenoming can therefore lead to ion channel dysregulation, which for humans can result in severe medical complications that often necessitate interventions such as antivenom administration. Conversely, the discovery of highly potent and selective venom toxins with the capability of distinguishing between different isoforms and subtypes of ion channels has led to the development of beneficial therapeutics that are now in the clinic. This review encompasses the historical evolution of electrophysiology methodologies, highlighting their contributions to venom and antivenom research, including venom-based drug discovery and evaluation of antivenom efficacy. By discussing the applications and advancements in patch-clamp techniques, this review underscores the profound impact of electrophysiology in unravelling the intricate interplay between ion channels and venom toxins, ultimately leading to the development of drugs for envenoming and ion channel-related pathologies.

摘要

离子通道在多种生理过程中发挥着关键作用,包括神经传递和肌肉收缩。有毒生物利用离子通道的重要功能,通过在其毒液中产生毒素,这些毒素专门针对这些离子通道,以便在叮咬或蜇刺时促进猎物捕获。因此,中毒可导致离子通道失调,对人类而言,这可能会引发严重的医学并发症,常常需要诸如注射抗蛇毒血清等干预措施。相反,发现具有区分离子通道不同异构体和亚型能力的高效且选择性的毒液毒素,已促成了目前正在临床应用的有益疗法的开发。本综述涵盖了电生理学方法的历史演变,突出了它们对毒液和抗蛇毒血清研究的贡献,包括基于毒液的药物发现以及抗蛇毒血清疗效评估。通过讨论膜片钳技术的应用和进展,本综述强调了电生理学在揭示离子通道与毒液毒素之间复杂相互作用方面的深远影响,最终促成了用于中毒及离子通道相关病症的药物开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/f4a96d7f1811/fphar-14-1249336-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/1d63d892bf55/fphar-14-1249336-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/023316d6994d/fphar-14-1249336-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/f4a96d7f1811/fphar-14-1249336-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/1d63d892bf55/fphar-14-1249336-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/023316d6994d/fphar-14-1249336-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3d0/10484000/f4a96d7f1811/fphar-14-1249336-g003.jpg

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