150 



L. J. MULLINS 



i" / 'ii///,|iimuuiV , % >> 

 i + ., + S 



"M\ v 



H IOA 



il// a'///. 



^ *"||,|,HIV''«U**. +\ 



"4 







E/S 4.E 



: P H 3 + x* 



A7 f% \ A 

 AyiOT^^ '^CH-|\ A 



Fig. 14. (1) Hexamethonium at full extension (the trimethylammonium groupings 

 are viewed from slightly different angles to show the variation possible); (2) (+) tubo- 

 curarin viewed so as to show its largest profile, the parallel lines above and below the 

 molecule represent the walls of an interspace, with A and E sites shown; (4) shows 

 tubocurarine in a view at right angles to that shown in (2), the dotted plus charge 

 shown in the lower right is 10A further down the interspace than that charge shown 

 at the top. The methoxy-grouping shown is in the same plane as the upper positive 

 charge. The interspace radius is 6 A.; (5) /3-erythroidine in the same interspace as (4); 

 (3) the extension of decamethonium between two membrane interspaces. 



about receptor block, although there may be some contribution of the ether 

 oxygens and the carbonyl group to binding at the E sites. The quaternization 

 of this compound, by changing the N-bond angles, destroys the special shape 

 of the molecule and results in poor blocking agents. All of the powerful blocking 

 agents require large sized interspaces for fit (a size of about (Mg ++ ) 2 or 6 A.) 

 and have structural features that will cause a condensation in size of such inter- 

 spaces, or a shift of the interspace distribution to larger mean values. This, 

 as has been shown in Fig. 10, leads to a reduction in the number of interspaces 

 into which ACh will fit, with little or no change in the number of 'enzyme' 

 interspaces. 



Two ions, Mg ++ and Ca ++ , exhibit a special case of antagonism at the n-m-j 

 and it seems that while many types of reactions may be involved, the principal 

 steady state situation is conditioned by the tendency of Ca ++ to occupy inter- 



