The effects of Anemonia sulcata toxin II on vertebrate skeletal muscle

Abstract

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.

Loss of Na+ channel inactivation by anemone toxin (ATX II) mimics the myotonic state in hyperkalaemic periodic paralysis.

“…Although we were not able to produce paralysis in our toxin model, it has been induced by ATX II in the rat hemidiaphragm (Alsen et al 1981) and the frog semitendinosus (Khan et al 1986), with higher concentrations, longer exposure times, or increased toxin potency. Both species and fibre type differences may account for variations in potency among various preparations (Harris et al 1985). We have, however, shown by computer simulation that only a small additional increase in < Popen > is required to produce paralysis (Cannon, Brown & Corey, 1993).…”

“…A small proportion of non-inactivating sodium channels is sufficient to cause myotonia The principal finding of this study is the demonstration that both the electrical and the mechanical features of myotonia can be produced by a failure of inactivation in a relatively small proportion of sodium channels. Although it has been previously established that ATX II slows the relaxation of the twitch response (Alsen et al 1981), induces a hyperexcitable state with trains of repetitive action potentials (Erxleben & Rathmayer, 1984;Harris et al 1985), and disrupts the inactivation of sodium channels in patch-clamp recordings (Nagy, 1988), no previous investigations examined all these effects simultaneously. We now provide quantitative results that allow a correlation to be made between the extent of the alteration in sodium channel gating and the appearance of myotonia.…”

“…The after-discharges and prolonged relaxation were myotonic in origin, as opposed to neurogenic, because all bath solutions contained d-tubocurare. Many previous studies have focused on the increased duration of the action potential produced by ATX II (Alsen et al 1981;Erxleben &J Rathmayer, 1984;Harris et al 1985;Kahn, Lemeignan & Molgo, 1986). At low concentrations of toxin, the action potential duration was often indistinguishable from controls (cf.…”

“…Across different species and tissues, nerve and muscle preparations possess varying degrees of sensitivity and reversibility to the effects of ATX II. Tesseraux and co-workers have demonstrated that ATX II increases force, lengthens the duration of action potentials, and may produce repetitive firing in a variety of mammalian muscle preparations (Alsen, Harris & Tesseraux, 1981;Harris, Pollard & Tesseraux, 1985).…”

Lidocaine selectively blocks abnormal impulses arising from noninactivating Na channels

“…All, however, selectively reduce the inactivating tendency of Na + channels and thus produce a persistent Na + current and prolonged membrane depolarizations 45, 49. As shown by Cannon and Corey,7 toxin II (ATXII) from the sea anemone Anemonia sulcata alters the impulse behavior of muscle fibers in a way that is similar to that present in myotonia and that generally sensitizes skeletal muscle to procedures that raise intracellular Ca 2+ 23…”