STRUCTURE OF NERVE CELL MEMBRANES 155 



can always consider excitation and block equivalent to raising and lowering 

 the threshold. This is something that puzzles me somewhat. I am not sure these 

 things are always the same. I think one has to take into account threshold to 

 what, and what threshold one is talking about, because I think one can get 

 shifts in this level within a range that might be said not to actually change the 

 threshold. 



Another question has to do with the problem of blocking at the surface, 

 which I think, you felt was always the case. I wonder whether that is really 

 so because certainly one can get particular preparations where you have de- 

 stroyed this situation to some degree and still get evidence of a similar type 

 of effect on very specific cell particulates. I am not quite sure that one always 

 has to or can stick at the surface even though it is very tempting to do this 

 under these circumstances. 



One other question was the statement you made, I think at the beginning, 

 about a change occurring with the alcohols at about C-6. If I remember cor- 

 rectly, on peripheral nerve, wasn't there a change from hypo to hyper polar- 

 ization below that, quite a distinct and sharp change, I think? I wonder how 

 this would fit. 



Dr. Mullens: I do not think I can say very much about the thresholds going 

 up or down. I have given you a false impression if I gave you the impression 

 that this sort of treatment leads to anything but a further appreciation of the 

 difficulty in deciding just exactly what is going on in such a complicated struc- 

 ture. I am looking at one little hole among the millions that are around; these 

 are filled with all conceivable kinds of substances that are pushing and pulling 

 and tugging and twisting all different ways and the idea that, except in the 

 abstract, we can see what the whole picture is is certainly not a valid one. When 

 you talk about, for example, the relationship between metabolism and excit- 

 ability or function, you have to consider whether metabolism is supplying 

 entities which are influencing the membrane directly by being retained in these 

 pore structures. Substances that are retained will in general be only those that 

 find a happy home in this type of structure. 



About the difference between agents that block at the surface versus blocking 

 processes inside the cell, I think that there are an almost endless number of 

 susceptible internal structures in the nerve cell and other cells in general; I 

 think that to some extent this is what Gilbert Ling has in mind in proposing 

 that there is an internal structural network which binds ions. 



As to alcohols and the question of hyperpolarization or depolarization, this 

 is a very complicated story because most narcotics are hyperpolarizing agents 

 and it is very easy to show that you get a certain amount of increase in the 

 membrane potential when such substances are applied, but lower alcohols 

 (especially methanol) are strong depolarizing agents simply because they 

 take enormously high concentrations of this substance to get the right activity 

 to fill up the membrane spaces so that in the process of this you get quite a 



