STRUCTURE OF NERVE CELL MEMBRANES 139 



and are separated from each other by 2.0 A., a figure that might be considered 

 set by the roughness of the surface of the macromolecule, or its deviation from 

 a circular shape. A circle of 3.8 A. radius can be inscribed in the interspace 

 specified above and it seems likely that it was derived from an interspace con- 

 siderably larger, perhaps 4.8 A. This is so because of the great precision with 

 which DDT must be oriented with respect to the interspace, a fact that makes 

 larger interspaces much more probable sites for DDT. Very large interspaces 

 will, however, allow the penetration of DDT in other orientations and thus 

 result in the filling of the membrane with molecules that do not give a good fit 

 with the interspace. 



If peripheral nervous structures upon which DDT acts have the same rela- 

 tive permeabilities to Cl~, K + , and Na + as squid axons, then the mean inter- 

 space size shown previously (4.2 A.) may be expected to represent the mean 

 size for a DDT-sensitive membrane. It has been suggested that the DDT 

 molecule, to produce its effect, must occupy interspaces that are large compared 

 with the mean size (perhaps 4.8 A.). Since the effects produced by DDT de- 

 pend upon there being relatively few DDT-occupied channels and since all 

 interspaces are capable of oscillating through the entire range of possible sizes, 

 selectivity with respect to occupying only a small number of channels is ob- 

 tained if the molecular size is large compared with the mean. Selectivity is 

 demanded by the model because if, per unit of time, 20% of the interspaces can 

 be occupied by DDT in one case, and 0.2% in the other, a large fraction of the 

 membrane interspaces will be occupied with a small number of DDT molecules 

 per channel. In the second case, the change in interspace size distribution 

 occasioned by the introduction of DDT into a few large interspaces suffices 

 to insure the filling of already occupied channels. If DDT encounters a mem- 

 brane of a mean size somewhat larger than itself, a somewhat different reaction 

 may take place. From the discussion of narcosis it would appear that sub- 

 stances that are smaller than the mean interspace size are good blocking agents. 

 DDT is, however, so very insoluble that its appearance in the membrane in 

 concentrations necessary for narcosis might be expected to occur only in times 

 far longer than those of the experiment; as a first approximation the substance 

 would appear inert. Those DDT molecules reaching the membrane may be 

 expected to bind well to interspaces of appropriate size but a single molecule 

 is doubtless insufficient to prevent membrane molecules from undergoing 

 thermal motion such that the DDT becomes repeatedly bound and unbound. 

 The C — CI bond of the ethane part of the molecule is considerably weaker than 

 that of the p-Cl binding so that if the repeated straining of the molecule results 

 in some chemical reaction this may be expected to be the removal of an ethane 

 CI atom. The subsequent decomposition of the free radical would yield DDE, 

 and the substrate specificity of this reaction may be expected to conform with 

 the results shown earlier. 



