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

1 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. 2 OTX-3 (1-10 mu g 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. 3 OTX-3 decreased the amplitude of miniature end plate potentials (m.e.p.ps) but did not affect their frequency. 4 Extracellular recording of compound action potentials revealed that OTX-3 affected neither excitability nor conduction along intramuscular nerve branches. 5 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. 6 Membrane depolarization induced by OTX-3 was decreased about 70% in muscles pretreated for 30 min with 10 mu M tetrodotoxin. In contrast, muscles pretreated with 5 mu M mu-conotoxin GIIIA were completely insensitive to OTX-3-induced depolarization. 7 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 mu-conotoxin GIIIA. 8 OTX-3 is a novel type of sodium-channel activating toxin that discriminates between nerve and skeletal muscle membranes.