NERVE ACTIVITY 



the (qualitative) consequences of enzyme theory to receptors. 

 We cannot apply the same quantitative techniques because ex- 

 cept for actomyosin no receptor has ever been isolated and work 

 must be done for the most part with living cells. Thus we are 

 faced with the problem of permeability. Even if the question of 

 relative permeability were not harassing, we do not at this time 

 know the functional relationship between the activity and the 

 number of receptor-activator complexes (some authors have 

 tacitly assumed a direct proportionality). 



In regard to the promotion of activity, the receptor function 

 might be expected, by analogy, to be much more pronounced for 

 acetylcholine as compared to the ammonium ions of dimethyl- 

 aminoethyl acetate or, since hydrolysis does not appear to be in 

 volved here, to be more pronounced for quaternary as compared 

 to tertiary cations, in general. As is well known, this is in fact 

 the case — suitable quaternary ions depolarize cell membranes 

 whereas tertiary ions do not. Less known is that tertiary ions 

 are receptor inhibitors. They are bound but lack the pro- 

 motional feature necessary to bring about receptor activity. In 

 work with the electroplax, i.e., the electric cells of electric organs, 

 it was shown that a number of quaternary and tertiary cations 

 block the generation of electrical potential by inhibiting the 

 acetylcholine receptor rather than acetylcholinesterase (1,30). 

 This was the first experimental distinction between acetylcholin- 

 esterase and the long suspected receptor. The quaternary ions, 

 by reacting with the receptor, blocked the action potential and 

 also depolarized the cell membrane; the tertiary ions blocked 

 without depolarization. But the tertiary ions antagonized the 

 depolarizing effect of the quaternary ions. For example, car- 

 bamylcholine blocks the action potential with depolarization of 

 the membrane, but procaine blocks without depolarization. If a 

 cell is blocked with procaine, subsequent addition of the same 

 quantity of carbamycholine fails to produce a depolarization. 

 Larger quantities produce depolarization. Similarly, if a cell is 

 blocked with carbamylcholine, the addition of larger quantities 

 of procaine will restore the membrane potential. 



643 



