390 PRINCIPLES OF GENERAL PHYSIOLOGY 



if a propagated disturbance is produced at all, it is a maximal one, and it is 

 impossible to produce one of the smaller magnitude of those excited in the 

 refractory state. The question arises, then, whether these smaller disturbances 

 can be made greater by stronger stimuli. Adrian (1913) finds that this is 

 impossible. So that the magnitude of the disturbance is conditioned only by the 

 state of the nerve at the time. 



The refractory state which follows a second effective stimulus, applied during 

 the relative refractory state following a previous stimulus, is shorter than the 

 normal one. The duration of the refractory state is, therefore, dependent on the 

 magnitude of the disturbance. 



The refractory state is not merely a local effect at the point of application of 

 the stimulus, but is the same at any point in the nerve after the passage of the 

 propagate 1 disturbance (Bramwell and Lucas, 1911). 



Keith Lucas (1911) shows further that the refractory state is associated with 

 the propagated disturbance by the fact that a stimulus falling within the absolute 

 refractory period of a previous one does not prolong that refractory state, and :i 

 third stimulus is effective at the same interval of time after the first, whether the 

 second has been interpolated or not. 



Fatigiie. If we regard fatigue as that result of activity by which a cell is less 

 readily put into action again until a certain time for recovery has been allowed, 

 it is clear that the refractory state itself is one of fatigue. Under ordinary 

 conditions, however, the recovery is so rapid and complete that it is impossible to 

 demonstrate that a nerve is less excitable at the end of a long period of activity 

 than at the beginning. From certain experiments by von Baeyer (1902), it 

 appears that, in the absence of oxygen, signs of fatigue are to be detected ; while 

 the refractory period was found by Frohlich (1904) to be prolonged to O'l second 

 in the absence of oxygen. In view of the definite proof by A. V. Hill, that the 

 heat evolved is so minute as to make it very doubtful whether there is any 

 metabolism in the nerve fibre, it becomes necessary to consider for a moment what 

 are the experimental facts with regard to the effect of oxygen. The experiments 

 of von Baeyer showed that a region of nerve, exposed to currents of nitrogen or 

 hydrogen, failed to respond to induction shocks after some five hours' action. 

 The excitability returned in oxygen. This behaviour is quite similar to that 

 when a typical anaesthetic is used, so that it seems that the process may well be 

 the same. Von Baeyer (1902, 2) did not obtain any evidence that the time 

 required to produce the state of inexcitability was made shorter by continued 

 stimulation of the nerve. Thorner (1909), however, found that continuous 

 tetanic stimulation, in the absence of oxygen, caused an earlier appearance of 

 the inexcitable condition ; recovery took place, to a considerable extent, when 

 the excitation ceased, ivilhont the necessity of the presence of oxygen. 



It seems possible that the local effect of the current at the electrodes was not sufficiently 

 excluded in these experiments. Polarisation is not easily prevented. Anyone who has excited 

 the vagus nerve of the cat is familiar with the fact that the inhibitory effect on the heart 

 rapidly disappears during stimulation and that reappearance occurs when the electrodes are 

 moved to another spot on the nerve. The results of von Baeyer may possibly have been din- 

 to traces of impurity in the gases used, although they were purified by the usual chemical 

 methods. Exposure for five hours might enable an effect to be produced by traces which 

 would be incapable of detection. 



r On the other hand, since we must suppose that nerve fibre is living, it is 

 difficult to believe that it is absolutely devoid of respiratory activity. We know 

 that it requires a certain minimal amount of energy to start a disturbance ; but 

 the fact that this disturbance in normal nerve is propagated without diminution, 

 suggests a physical process, although it might be argued that energy is supplied 

 to it as it travels. In the latter case, it is conceivable that the energy-giving 

 material might require replacement by an oxidation process ; but we are again 

 met with the difficulty of the absence of heat production. A. V. Hill suggests 

 that oxygen acts by keeping the machine in order, as it were, somewhat as oil in 

 a motor does. 



It must be confessed that this seems a rather unusual function for oxygen to perform, and 

 it does not appear to me that the dependence of excitability on oxygen has been satisfactorily 



