400 PRINCIPLES OP GENERAL PHYSIOLOGY 



histological evidence of any difference between the fibres in the trunk of the nerve and 

 their endings on the muscle. It is evident that the intermediate substance, on which 

 adrenaline acts, lies on the muscle side of the place of entry of the nerve fibre. Elliott 

 speaks of it as the "myo-neural" junction (1905, p. 43<j). 



Further light is thrown on the question by Langley's work on the antagonism 

 between nicotine and curare (1906). Nicotine, in fairly large doses, acts like 

 curare in preventing excitation of a motor nerve from reaching the contractile 

 substance of the muscle. In the fowl, 10 to 15 mg. suffices. The first effect of the 

 injection is to cause contraction of the muscles ; but the remarkable thing is, that, 

 after a dose which paralyses the nerve action, direct application of the drug to tin- 

 muscle itself still causes tonic contraction. Further, this effect is abolished by 

 curare. There is, in fact, a quantitative antagonism between the two substain e& 

 If nicotine be given after a dose of curare sufficient to paralyse the effect of nerve 

 stimulation, a tonic contraction is caused. Repeated doses of nicotine finally 

 paralyse the structures at first excited by it, although the muscle is still excitable 

 to electrical stimulation ; this is a further proof of some intermediate substance. 

 As we have seen, curare acts on something on the muscle side of the nerve ending 

 and nicotine must also act on the same substance. This constituent of the neuro- 

 muscular system, which is not the contractile substance of the muscle nor the 

 excitable substance of the nerve, is called by Langley the "receptive substance." 

 It receives the stimulus from the nerve and transmits it to the contractile 

 mechanism of the muscle. 



We may now consider the evidence brought by Keith Lucas from a different 

 point of view. In making experiments on the excitation of muscles with condenser 

 discharges to find the constant called by Waller the "characteristic," Lucas 

 (1906, 1) found that there were two distinct optimal stimuli, in one of which the rate 

 of incidence is represented by 37 to 63 and in another of which it is represented by 

 1,780 to 19,300. After moderate doses of curare, these are both left present, 

 although that with the higher optimal rate of incidence of energy shows signs of 

 abolition, which is complete with large doses. It appears that we have to do with 

 something analogous to Langley's receptive substance or Elliott's myo-neural 

 junction. 



In further investigation, Lucas (1906, 2) found that the end of the sartorius 

 muscle which is free from nerves shows only one optimum, represented by 20 to 36. 

 The trunk of the sciatic nerve also has an optimal rate represented by 41 to 233 

 only. Muscle fibre, free from nerve endings, has, therefore, an excitable substance 

 (a) of low optimal rate. The nerve trunk has one (y) of slightly higher value. In 

 the middle of the sartorius there are at least two, detectable by the use of the 

 condenser ; there is the muscle itself as above (a) and another ($) of an extremely 

 high optimal stimulus, on the muscle side of the curare block. In later work 

 (1906, 3 and 1907, 1) it was found better to use currents of varying strengths and 

 durations in place of the condenser discharges, and curves were drawn correlating 

 the current strength just sufficient to excite with the current duration. In this 

 way, the three substances above mentioned were found in the middle region of the 

 sartorius. The current strength used was, in all experiments, such that its 

 necessary duration never exceeded 0-02 second. 



It was pointed out above (page 394) that the logarithm of the constant 6 of Hill's 



k 



modified Nernst formula of excitation is a function of - ,, which is itself a measure 



a'" 



of the rate at which the diffusion of the ions concerned in excitation takes place. 

 It is natural to suppose that the rate of incidence of energy in the optimal 

 stimulus will be related to this factor, and Keith Lucas calculates (1910, p. 245) 

 the values of log 6 for various excitable substances as follows : 



Substance (3 of sartorius - 2 



Motor nerve fibres 0-3 



Muscle fibre of sartorius -. 0'07 



Ventricular muscle of heart - 0005 



These are arranged in order of rate of diffusion of ions. Compare these with the 



