A sublethal dose of a post-synaptic blocking fraction of Naja siamensis venom was injected into the soleus muscle of the mouse inhibiting neuromuscular transmission for 2-3 days. The paralysed soleus muscle behaved as if denervated, developing extra-junctional sensitivity to acetylcholine and accepting innervation by an implanted foreign nerve. Since the only known action of the postsynaptic blocking fraction of this venom is due to its affinity to acetylcholine receptors, the results suggest that the spread in the sensitivity of muscle fibres to acetylcholine and their ability to accept a foreign nerve is a consequence of neuromuscular blockade.The venoms of many elapid snakes are known to contain polypeptides with prolonged or irreversible curare-like activity at the neuromuscular junction [Lee, 1972]. The selective affinity of some of these polypeptides has been used to extract and purify acetylcholine (ACh) receptors from the electric organ of torpedo [Miledi, Molinoff and Potter, 1971;Karlsson, Heilbronn and Widlund, 1972]. The prolonged action of these compounds may also be used to study the effects of chronic post-synaptic blockade of neuromuscular transmission on skeletal muscle. In the present study sublethal doses of a neurotoxin of Naja siamensis venom with curare-like activity were injected into the soleus muscles of mice, causing prolonged block of neuromuscular transmission. After the muscles were paralysed they behaved as if denervated, suggesting that the preservation of certain physiological properties of skeletal muscle requires neuromuscular transmission to be intact.A preliminary account of these findings has already been published [Duchen, Heilbronn and Tonge, 1975].
METHODSSurgery. Adult albino mice of either sex were anaesthetized with an i.p. injection ((0 5g. kgof Avertin (Bayer Products Company) and the soleus muscle of the right leg exposed by dissection. Under directvision 3-5,ul of a solutioncontaining 1mg.ml-Iof the purified principal toxin of Naja siamensis venom [Karlsson, Arnberg & Eaker, 1971] dissolved in 1 % Na2HPO4 buffer (pH 6-6) containing 0-2 % gelatine was injected into soleus. The incisions were closed with clips. Up to 50 % of the mice died within 6 h of the injection of toxin.In 16 mice the common peroneal nerve (CPN) was cut and the proximal stump inserted into the part of soleus close to its proximal tendon (where there are no end-plates) two weeks *Present address: