NERVOUS ACTION 



mately equal to the internal. The total electric energy is, in this case, 

 about six times as high as the external, or about 48 X 10^® gcal. per 

 impulse per gram electric tissue (4). Under the same conditions and 

 tested simultaneously, the energy released by the breakdown of phos- 

 phocreatine was found to be about 32 X 10~^ gcal. per gram and im- 

 pulse (average of fifteen experiments). Lactic acid formation released 

 about 17 X 10^* gcal. per gram and impulse, averaging seven experi- 

 ments (13). The energy of lactic acid formation is probably used to 

 phosphorylate creatine just as in muscle, where phosphopyruvic acid 

 transfers its phosphate via adenosine triphosphate to creatine ("Parnas 

 reaction"). The figures are consistent with the conclusion that 

 energy-rich phosphate bonds are adequate to account for the energy 

 of the action potential. Hence, if the primary alterations of the 

 surface membrane during the passage of the impulse are due to the 

 release of acetylcholine, the figures suggest that phosphate bonds may 

 yield the energy for the synthesis of acetylcholine. 



The amounts of acetylcholine actually released during a dis- 

 charge are not known. But the amount which may be split by one 

 gram of electric tissue during one discharge — about 5 X lO"*^ milli- 

 mole — may be used as an indication. The amount actually released 

 may be smaller, since the enzyme may be present in excess, but the 

 figures indicate the order of magnitude. The amount of phospho- 

 creatine actually split per gram and impulse is about 3 X 10~^ milli- 

 mole. Thus, the amounts of acetylcholine and phosphocreatine 

 metabolized seem to be of the same order of magnitude. Since, 

 however, one mole of phosphocreatine yields about 10,000 gcal., while 

 the acetylation of choline requires probably not more than 1500 to 

 2000 gcal., the fate of the remaining energy has yet to be explained 

 (11). There are, of course, several conceivable processes which could 

 account for this diff'erence. For instance, with the splitting of acetyl- 

 choline, a simultaneous change of a protein molecule could occur, due 

 to the acid formed, by which the protein is brought close to its iso- 

 electric point. In such a case, the energy required for bringing the 

 protein molecule back to its original condition would be of an order of 

 magnitude similar to that available. But, so far, there is no experi- 

 mental evidence for this or any other simultaneous reaction. 



One of the essential facts supporting the new concept is, as 

 repeatedly emphasized, the extremely high concentration of choline 



345 



