{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:22:49Z","timestamp":1790713369156,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"REGION PAYS DE LA LOIRE (FRANCE)","award":["Pari Scientifique SODIVASC 2017"],"award-info":[{"award-number":["Pari Scientifique SODIVASC 2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thanks to the crosstalk between Na+ and Ca2+ channels, Na+ and Ca2+ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na+ (NaV) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca2+ concentration ([Ca2+]i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na+-Ca2+ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the NaV1.3 channel subtype, which likely endorses their voltage-activated Na+ currents. Notably, these Na+ currents were blocked by ICA-121431 and activated by the \u03b2-scorpion toxin Tf2, two selective NaV1.3 channel ligands. Using Fura-2, we showed that VTD induced a [Ca2+]i increase. This effect was suppressed by the selective NaV channel blocker tetrodotoxin, as well by the selective L-type CaV channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a NaV channel blocker, abolished VTD-induced [Ca2+]i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between NaV and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins.<\/jats:p>","DOI":"10.3390\/ijms23020827","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"L\u00e9a","family":"R\u00e9thor\u00e9","sequence":"first","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohee","family":"Park","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5100-5571","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Montnach","sequence":"additional","affiliation":[{"name":"Institut du Thorax, Universit\u00e9 de Nantes INSERM UMR 1087-CNRS UMR 6291, 44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Nicolas","sequence":"additional","affiliation":[{"name":"Institut du Thorax, Universit\u00e9 de Nantes INSERM UMR 1087-CNRS UMR 6291, 44007 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-2255","authenticated-orcid":false,"given":"Joseph","family":"Khoury","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"},{"name":"Department of Biology, Faculty of Science III, Michel Slayman Tripoli Campus, Lebanese University, Tripoli 1352, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Le Seac\u2019h","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Mabrouk","sequence":"additional","affiliation":[{"name":"Institut de Chimie Radicalaire, UMR CNRS 7273, Aix-Marseille Universit\u00e9, 13013 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold","family":"De Pomyers","sequence":"additional","affiliation":[{"name":"Latoxan Laboratory, 26800 Portes l\u00e8s Valence, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2881-2962","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Tricoire-Leignel","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-2611","authenticated-orcid":false,"given":"C\u00e9sar","family":"Mattei","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-0285","authenticated-orcid":false,"given":"Daniel","family":"Henrion","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6502-3110","authenticated-orcid":false,"given":"Ziad","family":"Fajloun","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science III, Michel Slayman Tripoli Campus, Lebanese University, Tripoli 1352, Lebanon"},{"name":"Laboratory of Applied Biotechnology (LBA3B), Azm Centre for Research in Biotechnology and Its Application, EDST, Lebanese University, Tripoli 1300, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9615","authenticated-orcid":false,"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"Institut du Thorax, Universit\u00e9 de Nantes INSERM UMR 1087-CNRS UMR 6291, 44007 Nantes, France"},{"name":"Laboratory of Excellence Ion Channels, Science & Therapeutics, 59650 Villeneuve d\u2019Ascq, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Legendre","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-7059","authenticated-orcid":false,"given":"Christian","family":"Legros","sequence":"additional","affiliation":[{"name":"INSERM, CNRS, MITOVASC, Equipe CarME, SFR ICAT, University of Angers, 49000 Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","unstructured":"Hille, B. 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