The marine polyether gambierol enhances muscle contraction and blocks a transient K+ current in skeletal muscle cells

Sébastien Schlumberger, Gilles Ouanounou, Emmanuelle Girard, Makoto Sasaki, Haruhiko Fuwa, M. Carmen Louzao, Luis M. Botana, Evelyne Benoit, Jordi Molgó

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    Gambierol is a complex marine toxin first isolated with ciguatoxins from cell cultures of the toxic dinoflagellate Gambierdiscus toxicus. Despite the chemical complexity of the polycyclic ether toxin, the total successful synthesis of gambierol has been achieved by different chemical strategies. In the present work the effects of synthetic gambierol on mouse and frog skeletal neuromuscular preparations and Xenopus skeletal myocytes have been studied. Gambierol (0.1-5 μM) significantly increased isometric twitch tension in neuromuscular preparations stimulated through the motor nerve. Less twitch augmentation was observed in directly stimulated muscles when comparing twitch tension-time integrals obtained by nerve stimulation. Also, gambierol induced small spontaneous muscle contraction originating from presynaptic activity that was completely inhibited by d-tubocurarine. Gambierol slowed the rate of muscle action potential repolarization, triggered spontaneous and/or repetitive action potentials, and neither affected action potential amplitude nor overshoot in skeletal muscle fibers. These results suggest that gambierol through an action on voltage-gated K+ channels prolongs the duration of action potentials, enhances the extent and time course of Ca2+ release from the sarcoplasmic reticulum, and increases twitch tension generation. Further evidence is provided that gambierol at sub-micromolar concentrations blocks a fast inactivating outward K+ current that is responsible for action potential prolongation in Xenopus skeletal myocytes.

    Original languageEnglish
    Pages (from-to)785-791
    Number of pages7
    JournalToxicon
    Volume56
    Issue number5
    DOIs
    Publication statusPublished - 2010 Oct

    Keywords

    • Action potentials
    • Frog neuromuscular preparation
    • Gambierol
    • Membrane potential
    • Mouse skeletal neuromuscular preparations
    • Muscle contraction
    • Potassium currents
    • Xenopus skeletal myocytes

    ASJC Scopus subject areas

    • Toxicology

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