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Selective depolarization of the muscle membrane in frog nerve‐muscle preparations by a chromatographically purified extract of the dinoflagellate Ostreopsis lenticularis

Meunier FA, Mercado JA, Molgo J +2 more1997British Journal of PharmacologyJournal Article

Abstract

The actions of a chromatographically identified extract of the marine dinoflagellate Ostreopsis lenticularis, named ostreotoxin‐3 (OTX‐3), were studied on frog isolated neuromuscular preparations. OTX‐3 (1–10μg ml−1) applied to cutaneous pectoris nerve‐muscle preparations depolarized skeletal muscle fibres and caused spontaneous contractions. The depolarization was neither reversed by prolonged washing nor by (+)‐tubocurarine. OTX‐3 decreased the amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their frequency. Extracellular recording of compound action potentials revealed that OTX‐3 affected neither excitability nor conduction along intramuscular nerve branches. End‐plate potentials (e.p.ps) elicited by nerve stimulation were reduced in amplitude by OTX‐3 and even showed reversed polarity in junctions deeply depolarized by the toxin. Membrane depolarization induced by OTX‐3 was decreased about 70% in muscles pretreated for 30min with 10μm tetrodotoxin. In contrast, muscles pretreated with 5μm μ‐conotoxin GIIIA were completely insensitive to OTX‐3‐induced depolarization. OTX‐3 did not affect e.p.p. amplitude and the quantal content of e.p.ps in junctions in which muscle depolarization was abolished by μ‐conotoxin GIIIA. OTX‐3 is a novel type of sodium‐channel activating toxin that discriminates between nerve and skeletal muscle membranes.

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