STRUCTURE OF NERVE CELL MEMBRANES 



145 



DFP Normal Curare 



DMEA ACh 



PrCh 



Diameter of Site 



Fig. 10. The number of vacant interspaces is plotted against their size for a nor- 

 mal membrane (solid line), for a membrane where the mean interspace size has been 

 decreased (DFP), and for a membrane where the mean interspace size has been in- 

 creased (Curare). Receptor-sized interspaces for ACh are indicated by the vertical 

 bar, enzyme sites by the area to the right of the bar. Along the abscissa is shown the 

 relative profile size of analogs of ACh, (dimethylaminoethyl acetate, and propionyl, 

 butyryl, and benzoyl choline) in an orientation suitable for enzyme action. It is not 

 suggested that receptor action for these analogs can be predicted from the curve, but 

 that one must expect marked penetration barriers for higher homologs. 



and enzyme. If, at the entrance to an interspace, a membrane molecule has 

 esteratic (E) and anionic (A) sites in alternation every 60°, two possibilities 

 are distinguishable: (a) the membrane molecules rotate freely about their 

 long axis, and (b) the molecules are non-rotating. The first arrangement gives 

 rise to sites: AAA, AAE, AEE, and EEE, while the latter gives only AAA and 

 EEE sites as shown in Fig. 11. It is also possible that an unknown or inactive 

 site X is present so that for non-rotating molecules the pattern is AEX. A 

 variety of experimental observations suggest, however, that at 30° intervals 

 around a membrane molecule a pattern AEA is repeated, giving rise to the 

 rather complex distribution shown in Fig. 11. This arrangement has the advan- 

 tage that the distance between A and E centers is about that in ACh, when the 

 macromolecule is 20 A in radius. The validity of this model may be tested by 

 comparing the fit of models of various substances with the results from enzyme 

 inhibition. With the simple quaternary ammonium ions, tetraethylammonium 

 ion is bound somewhat more firmly than tetramethylammonium ion (TMA) 

 although not as strongly as one might expect from the increase in dispersion 

 forces (Bernhard, 1955). Such binding studies do not take into account any 

 dispersion in site size, a factor that may be of considerable importance. Some 

 information on how TMA ought to be oriented is obtainable from a study 

 (Wilson, 1951b) where it was shown that ACh-ase blocked with TMA still 

 permitted the rapid reaction of thiolacetic acid with water. A further suggestion 

 regarding TMA orientation is the fact that this substance is stimulating in 

 its action on nervous structures, an effect not to be expected if the ion interacted 



