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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
Author(s) -
Meunier Frédéric A,
Mercado José A,
Molgó Jordi,
Tosteson Thomas R,
Escalona de Motta Gladys
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701256
Subject(s) - depolarization , tetrodotoxin , biophysics , hyperpolarization (physics) , chemistry , marine toxin , sodium channel , membrane potential , skeletal muscle , extracellular , anatomy , stimulation , toxin , biology , biochemistry , sodium , endocrinology , stereochemistry , organic chemistry , nuclear magnetic resonance spectroscopy
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 10μ m tetrodotoxin. In contrast, muscles pretreated with 5μ m 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.