Gambierol blocks a K$^+$ current fraction and affects action potential duration and the firing rate in rat fetal chromaffin cells
Autor: | Molgó, Jordi, Bournaud, Roland, Schlumberger, Sébastien, Sasaki, Makoto, Fuwa, Haruhiko, Benoit, Evelyne |
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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), 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), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Department of Biomolecular Sciences, Graduate School of Life Sciences, Tohoku University [Sendai], Chuo University (Chuo University), This study was supported in part by the project ALERTOX-NET (EAPA_317/2016), funded by the Interreg Atlantic program, and in part by the CNRS., The International Society for the Study of Harmful Algae (ISSHA), Band Schmidt C.J., Rodríguez Gómez C.F. |
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: | |
Zdroj: | 19th ISSHA International Conference on Harmful Algae ICHA2021-19th ISSHA International Conference on Harmful Algae ICHA2021-19th ISSHA International Conference on Harmful Algae, The International Society for the Study of Harmful Algae (ISSHA), Oct 2021, La Paz, Baja California Sur (Virtual event), Mexico. pp.199-204, ⟨10.5281/zenodo.7035142⟩ |
DOI: | 10.5281/zenodo.7035142⟩ |
Popis: | The dinoflagellate genus Gambierdiscus, particularly Gambierdiscus toxicus is known to produce numerous ladder polycyclic ether compounds, including gambierol, characterized by a transfused octacyclic polyether core, as well as the identified ciguatoxins responsible for ciguatera poisoning. Gambierol inhibits voltage-gated K+ (KV) channels in various mammalian excitable and nonexcitable cells, and motor nerve terminals of the neuromuscular junction. In the present study, we investigated the action of gambierol on outward K+ currents of cultured rat fetal adrenal medulla chromaffin cells using the whole-cell configuration voltage-clamp method. The pharmacological dissection of the outward K+ current, using selective K+ channel inhibitors, revealed that gambierol reduced just a small fraction of the total outward current without affecting calcium-activated K+ currents that were sensitive to apamin and iberiotoxin, and ATP-sensitive K+ currents sensitive to glibenclamide. Cultured fetal chromaffin cells were excitable and generated either evoked (upon direct electric stimulation) or spontaneous action potentials. These action potentials were sensitive to tetrodotoxin that blocks voltage-gated Na+ (NaV) channels. Gambierol neither affected the rising phase nor the overshoot of action potentials but significantly prolonged their repolarizing phase and increased the firing rate of action potentials during sustained current depolarization, as determined using current-clamp recordings. Our results highlight the effects of gambierol on KV channels and on the electrical properties of rat fetal chromaffin cells. It is likely that gambierol may cross the placental barrier as ciguatoxins do. Further studies are needed to determine whether such actions may have deleterious effects on fetuses. |
Databáze: | OpenAIRE |
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