Gambierol enhances evoked quantal transmitter release and blocks a potassium current in motor nerve terminals of the mouse neuromuscular junction

Autor: Jordi Molgó, Sébastien Schlumberger, Makoto Sasaki, Haruhiko Fuwa, Louzao, Carmen M., Botana, Luis M., Denis Servent, Evelyne BENOIT
Přispěvatelé: Service d'Ingénierie Moléculaire pour la Santé (ex SIMOPRO) (SIMoS), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University [Sendai], Departamento de Farmacología, Facultad de Veterinaria, Universidade de Santiago de Compostela [Spain] (USC ), SIMOPRO, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hess P. (Ed.), International Society for the Study of Harmful Algae (ISSHA) and Institut Francais de Recherche pour l'Exploitation de la Mer (Ifremer), in cooperation with the Intergovernmental Oceanographic Commission of the United Nations Educational, Scientific and Cultural Organization (IOC UNESCO), BENOIT, Evelyne, Hess P. (Ed.), International Society for the Study of Harmful Algae (ISSHA) and Institut Francais de Recherche pour l'Exploitation de la Mer (Ifremer), in cooperation with the Intergovernmental Oceanographic Commission of the United Nations Educational, Scientific and Cultural Organization (IOC UNESCO), Universidad de Santiago de Compostela [Spain] (USC)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Harmful Algae 2018 – from ecosystems to socio-ecosystems
Hess P. (Ed.), International Society for the Study of Harmful Algae (ISSHA) and Institut Francais de Recherche pour l'Exploitation de la Mer (Ifremer), in cooperation with the Intergovernmental Oceanographic Commission of the United Nations Educational, Scientific and Cultural Organization (IOC UNESCO). Harmful Algae 2018 – from ecosystems to socio-ecosystems, pp.147-150, 2020
HAL
Popis: In recent years, a great interest was developed to synthetize biologically-active natural products of marine origin. This is due to both their complex molecular structures and chemical diversity, and also to their unique biological activities. Among ladder-shaped toxins, gambierol, originally isolated from cultured Gambierdiscus toxicus dinoflagellate cells, together with ciguatoxins, has been successfully synthesized permitting detailed analyses of its mode and mechanism of action. Gambierol and analogs are known to inhibit some voltage-gated K+ (Kv) channel subtypes in various cell types. The aim of the present study was (i) to investigate whether gambierol has an action on quantal transmitter release evoked by nerve impulses and (ii) to determine whether Kv channels in motor nerve terminals of the mammalian neuromuscular junction are sensitive to the toxin action. Using electrophysiological techniques, the results obtained show that gambierol (2-20 nM) had no significant action on the resting membrane potential of mouse hemidiaphragm muscle fibers. In addition, spontaneous quantal transmitter release, measured by recording spontaneous miniature endplate potential frequency, remained unaffected by gambierol in resting neuromuscular junction. Gambierol (2 nM) increased about eight-fold the mean quantal content of evoked endplate potentials, as determined at individual junctions of the phrenic-hemidiaphragm preparation equilibrated in a low-Ca2+ and high-Mg2+ medium. The ability of gambierol to enhance quantal transmitter release was related to the reduction of a fast K+ current in nerve terminals. Overall, the present results show for the first time that gambierol enhances evoked quantal transmitter release in response to nerve stimuli, suggesting that it can be used to reverse pre- or post-synaptic neuromuscular blockade.
Databáze: OpenAIRE
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