Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells
In: ISSN: 1661-6596, 2022
academicJournal
Zugriff:
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 β-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.
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Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells
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Autor/in / Beteiligte Person: | Réthoré, Léa ; Park, Joohee ; Montnach, Jérôme ; Nicolas, Sébastien ; Khoury, Joseph ; Le Seac’h, Elodie ; Mabrouk, Kamel ; de Pomyers, Harold ; Tricoire-Leignel, Hélène ; Mattei, César ; Henrion, Daniel ; Fajloun, Ziad ; de Waard, Michel ; Legendre, Claire ; Legros, Christian ; MitoVasc - Équipe CarME (Cardiovascular Pathophysiology) (MITOVASC-CARME) ; MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC) ; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Institut du Thorax Nantes ; Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM) ; Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) ; Institut de Chimie Radicalaire (ICR) ; Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS) ; Azm Center for research in biotechnology and its applications, TRIPOLI ; Libanaise, Université |
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Zeitschrift: | ISSN: 1661-6596, 2022 |
Veröffentlichung: | HAL CCSD ; MDPI, 2022 |
Medientyp: | academicJournal |
DOI: | 10.3390/ijms23020827 |
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