EXCITATION AND INHIBITION 393 



according to the extent of the loss of impermeability at the excited spot. This 

 is why the electrical response of nerve or mtiscle may be called, as by its discoverer, 

 Du Bois Reymond, the " negative variation " ; negative does not refer to the sign 

 of the electrical response, but means diminution. 



This manner of origin of the electrical response is sometimes described as a 

 "concentration battery," but, if the description on pages 190-191 above be re- 

 ferred to, it will be seen that a concentration battery in the original sense requires 

 electrodes of one of the elements of the dissociated salt. The electromotive force 

 of the kind of battery with which we are here concerned is also a function of 

 the relative concentration of the two solutions in the ion to which the membrane 

 is permeable, and is expressed by the formula which Nernst worked out for the 

 concentration battery proper, as will be shown in Chapter XXII. 



If a potential difference is applied to such an arrangement, so that, for example, 

 the anode is on that side of the membrane where are the cations, to which we will 

 suppose the membrane to be impermeable, and the cathode on the opposite side, it 

 will be clear that no current will flow, since no cations can travel to the cathode to 

 be discharged there. The membrane is said to be polarised. If, however, the 

 membrane becomes completely permeable, the current can pass freely, and the 

 polarisation ceases. This change was shown by Hermann (1879, pp. 165-167) to 

 occur in the excitation of nerve; it becomes less polarisable, as it might be expressed. 



The fact may also be stated in the form that the excitatory change is increased at the 

 anode, diminished at the cathode. Verzar (1912) has obtained results which show that this 

 diminished polarisability lasts considerably longer than the electrical excitatory change proper, 

 although in a considerably diminished degree. 



Further direct evidence of increased permeability of the membrane in excitation 

 will be found in the case of muscle below. 



Confirmation of this view of the source of the electromotive force of nerve is to 

 be found in the experiments of Macdonald (1900) on the magnitude of the 

 "demarcation current," when immersed in solutions of electrolytes. This " demarca- 

 tion current " or potential difference between cut end and normal surface follows 

 the Nernst formula for concentration batteries, as we have seen that the membrane 

 process of the hypothesis in question does. 



It must be confessed that it is difficult to make out at present which of the two changes 

 referred to is the cause of the other, or whether they are different expressions of the same 

 phenomenon. The loss of impermeability may be the cause of the disappearance of polarisa- 

 tion, or the disappearance of polarisation, as in excitation by an electrical current, may affect 

 the membrane, which must be colloidal in nature, in such a way as to make it permeable. But 

 it is not easy to see how mechanical stimuli can directly affect polarisation. 



When the excitability of nerve is spoken of as a colloidal phenomenon, what is to be 

 understood is that the membranes of which we have spoken are of complex colloidal structure 

 and, as such, sensitive to electrolytes, etc. Hoeber (1910) has shown that electrolytes, in their 

 action on nerve, follow the Hofmeister series, a characteristic of their action on lyophile 

 colloids, as w^ have seen. Loewe (1913), also, shows how the action of narcotics is to be 

 explained as a (decrease of the possibility of the membrane becoming permeable on excitation. 

 This decrease is due to adsorption of the narcotic by the preponderant lipoid constituents 

 of the membrane, which are thus changed from lyophile to lyophobe colloids. 



The Nernst Theory of Excitation. Nernst (1899), considering the reasons why 

 ery rapidly alternating currents do not excite nerves, was led to the view that the 

 rocess of excitation by an alternating electrical current is essentially connected 

 h the production at some membrane of a certain minimal concentration of ions 

 to which the membrane is impermeable. If the time during which the current 

 passes in any one direction is too short, the opposite current will carry back these 

 ions before they have had time to reach the effective concentration. This view 

 leads to the simple law that single currents of variable duration will be of the same 

 just effective strength if the product of their strength and the square root of their 

 duration is constant. This follows from the mathematical expression for diffusion. 

 Now, experimentally, this simple relation is found to hold only in a limited region 

 of very short durations of current flow. In fact, Nernst himself regards it only as 

 a first approximation and suggests factors that have to be taken into consideration 

 in a law of wider application. Some of these factors have been considered by 

 A. V. Hill (1910) and modified formulae put forward. 



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