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 × 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 by interacting with the channel ‘gate’.