148 



L. J. MULLINS 



A " A 



Fig. 13. (1) A 20-2 (radius 4 A.) interspace occupied by diethylphosphoryl-; (2) 

 the same interspace occupied by di-isopropylphosphoryl- (from DFP), the E sites 

 are occluded; (3) an interspace of radius 5 A occupied by eserine; (4) the same inter- 

 space occupied by neostigmine. 



accommodate ACh-ase inhibitors, and because inhibitors of the receptor re- 

 quire interspaces of even larger size, it is possible that the membrane at the 

 n-m-j has a much larger mean size than that of axons, or that the dispersion 

 of interspace sizes is very much greater for this membrane. This latter situation 

 appears to offer better possibilities of explaining the action of various sub- 

 stances, and can be examined in some detail by studies on the inhibition of the 

 ACh receptor. 



When a single molecule has two quaternary ammonium ions separated from 

 each other by a CH 2 chain of n carbon atoms, the possible modes for binding, 

 with respect to the model are: (a) across the interspace between any two pairs 

 of A sites, (b) along the interspace channel, one pair of A sites near the surface 

 and another at some definite distance down the channel, (c) between the anionic 

 sites of two adjacent interspaces, and (d) one cationic nitrogen is not bound and 

 the molecule occupies the interspace in a variety of orientations. Undoubt- 

 edly many of these possibilities are realized to some extent, and the task of 

 specifying a particular orientation is made correspondingly difficult. To recog- 

 nize the principal mode of binding of a particular substance, certain tests can 



