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 microg 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 microM tetrodotoxin. In contrast, muscles pretreated with 5 microM 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.
Meunier
F A
FA
Laboratoire de Neurobiologie Cellulaire et Moléculaire, Centre National de la Recherche Scientifique (U.P.R. 9040), Gif sur Yvette, France.
Mercado
J A
JA
Molgó
J
J
Tosteson
T R
TR
Escalona de Motta
G
G
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D020916:Conotoxins; D004141:Dinoflagellida / Q000737:chemistry*; D008387:Marine Toxins / Q000302:isolation & purification / Q000494:pharmacology*; D009045:Motor Endplate / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000302:isolation & purification / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011893:Rana esculenta; D015222:Sodium Channels / Q000187:drug effects
D020916:Conotoxins; D008387:Marine Toxins; D009467:Neuromuscular Depolarizing Agents; D010456:Peptides, Cyclic; D015222:Sodium Channels; C108235:ostreotoxin 3; C046101:conotoxin GIII