NERVE ACTIVITY 



The vast amount of biochemical data accumulated, the 

 energetics, and the many correlations between chemical and 

 electrical events indicate the primary role of the acetylcholine 

 system. But it is naive to believe that we should therefore be 

 able to predict or explain all the electrical phenomena of the 

 intact cell. It would be tedious to enumerate even the known 

 factors involved about which we have little or no information. 

 Let us just discuss one or two as an illustration. What are the 

 molecular changes in the membrane which occur during the 

 action potential and how do they increase the permeability to 

 sodium ion? The picture of acetylcholine action mentioned 

 above is just one possibility. How many obstacles, on a molec- 

 ular level, have to be changed by chemical reactions in the 

 pathway of sodium ions moving from the outside to the cell 

 interior? How many receptors have to be activated in a single 

 pathway in order to obtain a propagated spike, how many have 

 to be inactivated to block it? Apparently only a small fraction 

 of the neuronal surface is active at any given time. But are 

 these always the saine foci or are there many alternatives? We 

 can estimate that one molecule of acetylcholine released permits 

 the passage of at least 400 sodium ions. But is it not possible 

 that three to five molecules located at a certain distance in one 

 single pathway must be released either simultaneously or per- 

 haps in a special sequence to permit 1200 to 2000 sodium ions to 

 pass at any single point? 



If we apply our crude methods to the cell, we should not be 

 surprised if the reaction does not correspond to expectations on 

 the basis of the known in vitro properties of the system or, more 

 correctly, of part of the system. The use of microelectrodes in- 

 serted into a single fiber is a step forward compared with the tech- 

 niques of the 19th century. This method made it possible to 

 demonstrate with a suitable preparation and under appro- 

 priate experimental conditions that mono- and di-quaternary 

 compounds such as acetylcholine and curare may affect not only 

 synaptic transmission but also the propagated spike (1), as was 

 postulated on the basis of chemical studies. It took a century, 



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