SELECTIVE DEPOLARIZATION OF THE MUSCLE MEMBRANE IN FROG NERVE-MUSCLE PREPARATIONS BY A CHROMATOGRAPHICALLY PURIFIED EXTRACT OF THE DINOFLAGELLATE OSTREOPSIS-LENTICULARIS
Fa. Meunier et al., SELECTIVE DEPOLARIZATION OF THE MUSCLE MEMBRANE IN FROG NERVE-MUSCLE PREPARATIONS BY A CHROMATOGRAPHICALLY PURIFIED EXTRACT OF THE DINOFLAGELLATE OSTREOPSIS-LENTICULARIS, British Journal of Pharmacology, 121(6), 1997, pp. 1224-1230
1 The actions of a chromatographically identified extract of the marin
e 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 preparation
s depolarized skeletal muscle fibres and caused spontaneous contractio
ns. The depolarization was neither reversed by prolonged washing nor b
y (+)-tubocurarine. 3 OTX-3 decreased the amplitude of miniature end p
late potentials (m.e.p.ps) but did not affect their frequency. 4 Extra
cellular recording of compound action potentials revealed that OTX-3 a
ffected 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 depolarizatio
n induced by OTX-3 was decreased about 70% in muscles pretreated for 3
0 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 quant
al content of e.p.ps in junctions in which muscle depolarization was a
bolished by mu-conotoxin GIIIA. 8 OTX-3 is a novel type of sodium-chan
nel activating toxin that discriminates between nerve and skeletal mus
cle membranes.