Resistance to tetrodotoxin in toad sympathetic nerves

During an investigation of the innervation of the gut of the toad (Bufo marinus), it was found that the excitatory responses of the isolated small intestine to splanchnic nerve stimulation were resistant to blockade by a wide variety of autonomic blocking drugs, including the local anaesthetic drugs procaine and cinchocaine. To check whether this response was due to a direct spread of the stimulating current to the muscle, the drug tetrodotoxin was applied. Tetrodotoxin is known to prevent the specific sodium conductance change during the action potential in nerve fibres (Narahashi, Moore & Scott, 1964; Nakamura, Nakajima & Grundfest, 1965; Kao, 1966; Takata, Moore & others, 1966), and on the other hand it has only minimal effects on action potentials in vertebrate smooth muscles (Bulbring & Tomita, 1966; Kuriyama, Osa & Toida, 1966). Because of these properties it has been possible to use tetrodotoxin to give an effective “denervation” of vertebrate smooth muscle preparations (Gershon, 1966, 1967; Bulbring & Tomita, 1966; Bell, 1968), a concentration of 5 x lo-’ g/ml sufficing to do this. However, in the present experiments it was found that tetrodotoxin in doses of up to 5 x lo4 g/ml failed to cause any reduction of the contraction of the toad intestine caused by splanchnic nerve stimulation (Fig. 1). On the other hand, the response of the intestine was abolished by cutting the splanchnic nerves between the stimulating electrodes and the muscle.