312 PHYSIOLOGY 



previous chapter. Kiihne has shown that when the irritability of 

 the frog's sartorius is tested at different points it is greater in the 

 situation of the end- plates. This might be ascribed to the presence 

 of the more irritable nerve-fibres passing into the muscle-fibres at 

 these points. The unequal distribution of irritability is not, however, 

 changed when the muscle is fully poisoned with curare, so as to 

 block entirely the passage of any impulse from the nerve to the muscle. 

 We must therefore regard curare as acting, not on the axon terminations, 

 but on the substance intervening between these terminations and the 

 contractile substance of the muscle. Additional evidence of the 

 existence of such a " receptor " substance, as he calls it, has been 

 furnished by Langley. Nicotine resembles curare in blocking the 

 passage of impulses from the motor nerve to skeletal muscle, though 

 inferior to curare in this respect. If 4 mg. of nicotine be injected 

 into the vein of an anaesthetised fowl, the hind limbs become gradually 

 stiff and extended in consequence of a tonic contraction of all their 

 muscles. The effect slowly passes off, but can be reinduced by a 

 second dose of nicotine. It is worthy of note that the stimulating 

 effect of nicotine occurs even when sufficient is given entirely to paralyse 

 the motor nerves. It might be thought that the stimulating effect of 

 nicotine was a direct one upon the muscle fibre, but experiment shows 

 that curare has a marked antagonising action on the contraction pro- 

 duced by nicotine. A sufficient dose of curare annuls the contraction 

 produced by a small amount of nicotine and diminishes that caused by 

 a large amount. The point of action of the nicotine must therefore be 

 the same as that of the curare. After a muscle has been relaxed by 

 curare it can be still made to contract by direct stimulation. On the 

 other hand, nicotine will produce its stimulating effect when injected 

 into a bird in which degeneration of all the nerve fibres of the muscle 

 has been produced by previous section of the nerve-trunks. It is 

 evident therefore that nicotine, like curare, acts, not on the axon 

 terminations, but on a receptor substance, an intermediary substance 

 intervening between the axon terminations and the contractile sub- 

 stance of the muscle. 



Evidence in favour of such an intermediary substance has been 

 brought by Keith Lucas from an entirely different standpoint. In 

 determining the optimal electrical stimuli or the ' characteristic ' of 

 muscle and nerve by the condenser method (v. p. 305), Lucas finds that, 

 even after moderate doses of curare sufficient to abolish the possibility 

 of excitation through the nerve-trunk, the muscles show two optimal 

 stimuli, pointing to the existence in them of two excitatory substances, 

 one of which is not paralysed by moderate doses of curare. This 

 result was confirmed when the tissue was investigated by determining 

 the relation of current duration to the liminal current strength 



