1 Some effects of the sea-anemone toxin ATX-II on mammalian nerve-muscle preparations have been described. 2 When ATX-II (10 -8 10 -6M) was applied to rat hemidiaphragm preparations, both directly and indirectly generated twitch responses were potentiated and prolonged. At the same time the resting tension of the preparations increased. 3 The increase in resting tension caused by ATX-II in innervated muscles was not prevented by curarization, but was reversed by exposure to tetrodotoxin. The increase in denervated muscles was not completely reversed by tetrodotoxin.4 At concentrations exceeding 1 x 1 0-7 M, ATX-II caused a sodium-dependent depolarization of both normal and denervated muscles. The depolarization of the denervated muscles was only partially reversed by tetrodotoxin. S In the presence of ATX-II repetitive endplate potentials (e.p.ps) were evoked by single shocks to the motor nerves in many fibres, and in those in which a single e.p.p. was still observed, the quantum content (m) was increased. Miniature e.p.p. frequency was not increased by ATX-II, even when muscle fibres were depolarized by 30 mV. 6 The indirectly and directly elicited action potentials of normal and denervated muscle fibres were much prolonged by ATX-II. The action potentials remained sodium-dependent. The sodiumdependent tetrodotoxin-resistant action potential of the denervated muscle fibre was also prolonged by ATX-II. 7 It is concluded that ATX-II both activates, and delays inactivation of, sodium channels in mammalian skeletal muscle fibres, probably by interacting with the channel 'gate'.

Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE 1 Some effects of the sea anemone toxin, ATX-II, on vertebrate skeletal muscle have been described.2 At a concentration of 1 x IO-'-1 x 10-6M, ATX-I1 caused a sodium-dependent depolarizaton of the muscle fibres of the rat soleus and extensor digitorum longus, of the mouse soleus and extensor digitorum longus and of the chicken posterior latissimus dorsi. The muscle fibres of the frog sartorius were insensitive to the toxin. 3 Action potentials generated by direct stimulation were prolonged by ATX-II, but the degree of prolongation was variable. Chicken posterior latissimus dorsi muscle fibres were most sensitive in this regard, and mouse extensor digitorum longus were least sensitive. 4 Both denervated and immature muscle fibres were more sensitive to ATX-II than mature innervated muscle fibres. The sensitivity to ATX-II declined rapidly as muscle fibres matured. 5 In some muscles, the prolongation of the action potential was enhanced by repetitive stimulation, but not by the passive depolarization or hyperpolarization of the muscle fibres. 6 The actions of ATX-II could be reversed by washing in all but the innervated soleus of the mature rat.

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