468 ANNALS NEW YORK ACADEMY OF SCIENCES 



Although there are many instances of a close parallelism between 

 the stability of nerve, as measured by its electric threshold or by the 

 spontaneous development of impulses, and its rate of respiration, there 

 are exceptions. For instance, the rhythmic activity may be abolished 

 by the application of potassium chloride, which, at the same time, in- 

 creases the rate of respiration. Another instance of such a lack of 

 parallelism is revealed when a nerve is returned to its normal fluid 

 environment, after treatment with sodium citrate. The rhythmic ac- 

 tivity is promptly suppressed, and the threshold becomes normal, long 

 before there is a corresponding recovery of the original, normal rate 

 of respiration. 



IV 



There has been a persistent notion that the initiation of trains of 

 impulses from a chemically activated portion of an axon or from a 

 sense organ under a constant stimulus is due to a gradient of electric 

 potential at the site where the impulses originate. Indeed, Adrian^^ 

 found that there was a gradient of 10 mV between a normal portion of 

 nerve and an injured region from which impulses were discharged. 

 Accordingly, he attributed the excitation to this demarcation potential. 

 Furthermore, Erlanger and Blair^* and Fessard^^ caused the rhythmic 

 discharge of impulses by the passage of constant currents. Finally, 

 Katz^*^ and Arvanitaki^^ found that the duration of such an electrically 

 induced repetitive discharge could be much prolonged by reducing the 

 calcium content of the nerve. 



Because of these considerations, we have carefully searched for some 

 causal relation between a potential gradient developed at the site of 

 calcium removal and the chemical initiation of impulses. To do this, 

 one of a pair of non-polarizable electrodes was placed in contact with 

 the chemically altered region of the nerve; the second was in contact 

 with an adjacent, untreated portion. We have found that the activity 

 develops in the calcium-deficient part of the nerve, without the appear- 

 ance of an appreciable longitudinal potential gradient.^^ However, this 

 part of the nerve is very sensitive to weak currents. It is, therefore, 

 possible that potential differences of less than a millivolt might be in- 

 volved in the mechanism of chemical excitation. 



Accordingly, experiments were devised to study quantitatively the 

 relation between the frequency of conducted impulses and changes in 

 membrane polarization produced in the hyper-excitable portion of the 

 axon by certain additional chemical agents. Increasing the proportion 

 of potassium chloride in the solution of sodium citrate used to excite 



