VOL. 4 (1950) PERMEABILITY AND NERVE FUNCTION, II III 



some reactions have occurred which facihtate the more rapid loss of K by these libres. 



A short discussion of the methods employed in the papers of Hodgkin and Huxley 

 AND Keynes as compared with the present investigations might be of interest. The 

 method used by Hodgkin and Huxley involves measurement of the small changes 

 in the ionic conductivities over small areas of the nerve membranes before and after 

 activity. Both the electrical recording equipment and the electrode assemblies are 

 complex and the method employed necessitates numerous assumptions. The method 

 employed by Keynes is more direct. However, he has used multifibre preparations. 

 Under such circumstances, one could expect a retarded diffusion of K*^ away from the 

 nerve preparation because of the possible trapping of K in the intracellular fluids. Since 

 only the radioactivity of the K*- remaining in the nerve preparation was measured 

 in these investigations, one would expect that values obtained in this manner would 

 be higher than the actual intracellular K*^ content of the fibres. The calculated value 

 for the K leakage per cm^ per impulse would therefore be expected to be smaller than 

 the true value. 



The method employed in the present investigation is direct. Since it is possible 

 to analyse directly the axoplasm of the single nerve fibre, the values obtained must be 

 considered to be more precise than those obtained by either of the above methods. 

 The only assumption involved is the exact size of the individual fibres employed. How- 

 ever, since all of the Squid used were of approximately the same size, it is safe to assume 

 that the fibres were all of approximately the same diameters. For medium size Squid 

 this is approximately 500 fi (0.05 cm). It is justifiable to assume that the average value 

 is close to this figure. 



The investigation of the effect of inhibitors of acetylcholine-esterase on the rates 

 of the ion exchange across the nerve membrane requires some comment. It has been 

 shown that exposure of nerves to sea water for 30 minutes containing K^^ pj^s DFP 

 causes a decrease in the rate of K exchange from 1.31 to 1.08 millimoles per 100 g. The 

 exposure of nerves to DFP has apparently altered the permeability of the nerve mem- 

 brane. The DFP could conceivably have affected the membrane by decreasing its 

 permeability. However, the effect of DFP on the rate of Na penetration excludes this 

 interpretation. The value for the Na penetration markedly increased from 9.6 millimoles 

 Na per 100 g to 16.4 milUmoles upon the addition of 0.022 M DFP. If the DFP had had 

 the effect of decreasing the membrane permeability one would have expected a de- 

 creased Na exchange. It might have been expected that with increased ion permeability 

 the K could penetrate into the fibre more readily. However, since the concentration 

 of K inside of these nerves is approximately 20 times that of sea water, it is likely that 

 the easily exchangeable K will rapidly diffuse out into the sea water in an attempt to 

 equalize the adverse concentration gradient across the nerve membrane. The K, in 

 this case, will be replaced by the entrance of Na in order to maintain the electrical 

 neutrality of the axoplasm. In such an event, the exchange of K*^ would proceed at a 

 decreased rate and this obviously accounts for the decreased K exchange in the presence 

 of DFP. Thus, the Na and K exchange measurements are consistent with the concept 

 that the membrane permeability had been increased by the DFP. 



The probability of the exchange of K^^ for radioactive Na^* was discussed befoie. 

 Another factor to be considered is the constancy of the total cation content of these 

 nerves. It has been demonstrated by Steinbach and Spiegelman^ that under normal 

 resting conditions the cation content (Na -f K) of these nerves is a constant. However, 

 References p. 114. 



