Two peptides from tarantula venom inhibit the human voltage-gated proton channel by a unique mechanism

Two peptides from tarantula venom inhibit the human voltage-gated proton channel by a unique mechanism | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 19 June 2025 V1 Latest version Share on Two peptides from tarantula venom inhibit the human voltage-gated proton channel by a unique mechanism Authors : Ali Rahpeymaei , Sepideh Mehrabi1 , Agota Csoti , Jesus Angel Borrego Terrazas , Teklu Teshome Russo , Shahrukh Husain , Samuel Cardoso-Arenas , … Show All … , Herlinda Clement , Ivan Arenas , Gyorgy Panyi , Zoltan Varga , Gerardo Corzo , and Ferenc Papp 0000-0002-9549-6066 [email protected] Show Fewer Authors Info & Affiliations https://doi.org/10.22541/au.175034528.88010550/v1 418 views 156 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Spider venoms contain peptide toxins that modify ion channel currents, primarily in excitable insect cells. Research has revealed various peptides with pharmacological properties affecting mammalian species, including immune cell ion channels like the voltage-gated proton channel Hv1. This channel facilitates reactive oxygen species (ROS) production during the respiratory burst, contributing to inflammation and carcinogenesis by maintaining an acidic tumor microenvironment that supports tumor growth, invasion, and resistance to apoptosis. Experimental Approach: In this study, six animal venoms underwent screening against hHv1 using the patch clamp technique. The complete venom extracted from the spider Grammostola rosea resulted in the modulation of hHv1 expressed in CHO cells during whole-cell patch clamp measurements. HPLC reverse-phase fractionation of the venom showed that two peptide fractions #7 (GsAF-I) and #9 (GsAF-II) were active . Key Results: GsAF-I and GsAF-II inhibited Hv1 with micromolar Kd values in a membrane potential-dependent manner. Voltage ramp protocol revealed a shift in the Hv1 activation threshold toward a more positive potential. Voltage step protocol showed slowed activation kinetics and accelerated deactivation kinetics, suggesting stabilization of the closed state. The effects of both peptides were reversible. The membrane potential dependence of the inhibition was uniquely analysed and presented in this study. Conclusion and Implications: This is the first study to investigate in detail the inhibitory effect of peptides from animal venoms on the human Hv1 ion channel. The found two peptides effectively modify proton currents, highlighting their potential as lead compounds for drug development. Supplementary Material File (gsaf_manuscript.docx) Download 5.29 MB Information & Authors Information Version history V1 Version 1 19 June 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Ali Rahpeymaei University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Sepideh Mehrabi1 University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Agota Csoti University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Jesus Angel Borrego Terrazas University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Teklu Teshome Russo University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Shahrukh Husain University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Samuel Cardoso-Arenas Instituto de Biotecnologia - UNAM View all articles by this author Herlinda Clement Instituto de Biotecnologia - UNAM View all articles by this author Ivan Arenas Instituto de Biotecnologia - UNAM View all articles by this author Gyorgy Panyi University of Debrecen View all articles by this author Zoltan Varga University of Debrecen View all articles by this author Gerardo Corzo Instituto de Biotecnologia - UNAM View all articles by this author Ferenc Papp 0000-0002-9549-6066 [email protected] University of Debrecen Department of Biophysics and Cell Biology View all articles by this author Metrics & Citations Metrics Article Usage 418 views 156 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Ali Rahpeymaei, Sepideh Mehrabi1, Agota Csoti, et al. Two peptides from tarantula venom inhibit the human voltage-gated proton channel by a unique mechanism. Authorea . 19 June 2025. DOI: https://doi.org/10.22541/au.175034528.88010550/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . Format Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks Direct import Tips for downloading citations document.getElementById('citMgrHelpLink').addEventListener('click', function() { popupHelp(this.href); return false; }); $(".js__slcInclude").on("change", function(e){ if ($(this).val() == 'refworks') $('#direct').prop("checked", false); $('#direct').prop("disabled", ($(this).val() == 'refworks')); }); Cited by Jesús Borrego, Beáta Mészáros, Tibor Szanto, Russo Teshome, Éva Korpos, Zoltan Varga, Ferenc Papp, Modulators of the Human Voltage-Gated Proton Channel Hv1, Pharmaceuticals, 18 , 10, (1480), (2025). https://doi.org/10.3390/ph18101480 Crossref Loading... View Options View options PDF View PDF Figures Tables Media Share Share Share article link Copy Link Copied! Copying failed. 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