Mechanical and electrophysiological effects of sea anemone (Anemonia sulcata) toxins on rat innervated and denervated skeletal muscle.

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(-6) M) 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 10(-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. 5 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 sodium-dependent 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 in interacting with the channel "gate'.