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

摘要

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 (1–10 μg 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 30 min with 10 μM tetrodotoxin. In contrast, muscles pretreated with 5 μM 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.