112 M. A. ROTHENBERG VOL. 4 (1950) 



it is not known whether nerves in which the permeability has been increased still main- 

 tain their normal total cation concentration. It is possible that under these conditions 

 Na as well as CI may diffuse into the cell. This would result in increased total base 

 content. Since the total base content of the axoplasm samples has not been measured, 

 the contribution by the NaCl diffusion into the nerve cannot be evaluated. This problem 

 has to be investigated further. 



The effect of eserine, another inhibitor of acetylcholine-esterase had a similar but 

 less marked effect than DFP in increasing the membrane permeability to Na. It may 

 be noted, that in the case of DFP conduction was, on the basis of previous experience, 

 abolished irreversibly. In the case of eserine the effect was almost certainly still rever- 

 sible. 



The result obtained with acetylchoHne-esterase inhibitors, suggest that these sub- 

 stances may be capable of altering the membrane permeability. Since the only known 

 action of these compounds is the inhibition of the enzyme acetylcholine-esterase^^ 

 which is known to be closely connected with nerve conduction, it is possible that the 

 effect observed is a manifestation of the inactivation of the enzyme. These experiments 

 do not permit any definite conclusion, especially in view of the irreversible action of 

 DFP during the long exposure period used. However, they may open a new approach to 

 the importance of the acetylcholine-esterase system in the permeability of the surface 

 membrane to ions. 



The study of effects of cocaine on the membrane permeability to Na has indicated 

 a small increase in the rate of exchange. The data are inadequate to judge whether or 

 not this increase is significant. Employing the same concentration of cocaine (5 • io~^ M), 

 Shanes", from membrane potential measurements, came to the conclusion that a 

 decrease in permeability had been accomplished. The results obtained here fail to con- 

 firm his reports. 



The study of effects of irradiation of nerves with large doses of X-rays (50000 R 

 and 125000 R) indicates that immediately following exposure, marked alterations in 

 membrane permeability are evident. Exposure to 125000 R caused a large increase 

 in membrane permeability while 50000 R caused only a small but significant increase. 

 It should be noted that these studies were carried out immediately after irradiation. 

 It is possible that a more marked effect would be evident with smaller doses of irradiation 

 if longer periods of time were permitted to elapse between irradiation and exposure to 

 radioactive ions. From our present knowledge, it is clear that the most notable effects 

 of exposure to radiation occur after prolonged periods of time so that a longer time 

 lapse than that used in these experiments might be preferable. It appears significant that 

 it has been possible to demonstrate increased membrane permeability as result of X-ray 

 irradiation. 



I wish to express my gratitude to Dr David Nachmansohn for suggesting these 

 investigations and for the guidance and encouragement he has given throughout the 

 course of this research. I am indebted to Mrs Emily Feld-Hedal and Mrs Heidi 

 Richards for their assistance in the experiments. 



SUMMARY 



I. Studies on the permeability of the surface membranes of the giant axon of Squid to K indicate 

 that a dynamic rather than a static equilibrium exists at rest. Approximately 10% of the total K 



References p. 114. 



