The Nerve Trigger 



KENNETH S. COLE 



National Institutes of Health, Bethesda, Maryland 



THE NATURE OF NERVE ACTIVITY and the analogy to the operation of a 

 trigger mechanism have long been recognized, and the 'all-or-none law' 

 of excitation and propagation has come to be one of the fundamental principles 

 of physiology. The next questions have been: What is an adequate stimulus or 

 trigger 'pull,' and what does it release? 



It has often been assumed, and accumulated evidence strongly suggests that 

 a sufficiently large and rapid decrease of the electrical potential difference 

 across a nerve membrane may be the principal condition for the initiation of 

 nerve activity. Although an increasing emphasis has been placed on the search 

 for an electrochemical system which could be 'exploded' by such a 'trigger,' 

 crucial experiments of the past decade have clearly differentiated the physical 

 and the electrochemical components of the system. The electrochemical prob- 

 lems have been robbed of much accrued drama and glamour, but the questions 

 have been made highly specific and the answers of paramount importance. 



At the present stage of development, it cannot be overemphasized that in 

 the control of ionic flows across the nerve membrane there is nothing even re- 

 motely resembling a metastable state, and that of itself the ionic system is 

 completely incapable of reacting explosively. On the contrary, these ionic cur- 

 rents are quite docile, rather leisurely, and only slightly greedy in their re- 

 sponses to the controlling electrical potential. It is only with extreme provo- 

 cation, with an overwhelming and urgent drive, that they allow themselves to 

 be gotten into a position where, as they begin to give way, the pressure upon 

 them becomes even greater. But, at any and all times, upon the removal of this 

 pressure they also revert to the appropriate condition without any snap or jerk 

 and only as a sedate and dignified compliance with a gentle call. 



But if the ion movements of themselves are so complacent and entirely 

 cooperative, where lies the basis of the trigger-like sensitivity, the hard-hitting — 

 almost vicious — response that makes a nerve so effectual a channel of informa- 

 tion and control? It cannot be in the purely physical electrostatic capacity of 

 the nerve membrane. This seems to be a completely passive, utterly inert, 

 entirely linear and but slightly wasteful structural component under all condi- 

 tions. Strictly as ion pairs accumulate across it, it becomes stressed and the 

 electrical potential builds up and decreases only as the ion pairs disperse. 



The metastability and consequent explosive potentialities lie only in the 



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