THE NEURO-MUSCULAR JUNCTION 2 77 



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 produced 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 stimula- 

 tion. 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 termina- 

 tions, but on a receptor substance, an intermediary substance intervening 

 between the axon terminations and the contractile substance 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. 263), 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 necessary to excite. In a normal sartorius he finds 

 three substances, each distinguished by its own ' excitation time/ In the 

 pelvic nerve-free end of the sartorius there is only one substance with an 

 excitation time of -017 sec. This may be regarded as the muscle substance 

 proper. In the sciatic nerve-trunk there is a second substance with a much 

 steeper characteristic and with an excitation time of -003 sec. On experi- 

 menting on the middle region of the sartorius we find not only these two 

 substances but a third substance, which Lucas calls the substance (3, with 

 an extremely rapid excitatory process. Its excitation time is -00005 sec. 

 The presence of these three substances in the middle part of the toad's 

 sartorius is shown in the diagrams (Fig. 123), which represent the relation of 

 strength to duration of the currents necessary to evoke a contraction. In 

 this cuive a represents the muscle material, y the nerve material, and p the 

 curve of the intermediary substance. 



