118 MARTIN G. LARRABEE AND PAUL HOROWICZ 



common — that both of these tissues exhibit electrical activities — some experi- 

 ments we have done might throw a little bit of light on this problem. What 

 would happen if you inhibit the glycolysis and then inhibit the respiration 

 completely with almost 100% nitrogen? Under these conditions, after several 

 hours of treatment, the muscle obviously has lost its respiratory activity as 

 well as its mechanical activity. The question arises; where are the possible 

 sources the cells are still endowed with, since under such conditions if you keep 

 the cells at zero degrees they maintain not only their normal ionic composition, 

 but a full capacity to do electrical as well as mechanical work. Now, under such 

 conditions, we know there are three possible sources of energy; that is, with 

 the respiration and glycolysis both blocked. These sources are, of course, ATP 

 and creatine phosphate as well as unknown sources. There is a possibility of 

 checking and finding out what these unknown sources are. Some years ago Dr. 

 Hill and his colleagues did make measurements of the total energy that could 

 be liberated from such a system from the time the muscles were fully poisoned 

 to the time the muscles completely died, and these measurements showed the 

 total energy measured, since heat was very constant. This was later confirmed, 

 and was of the magnitude of about 0.42 calories per gram. I may have to change 

 the exact figure later, but it is constant per gram of wet weight. At that time 

 the free energy data were not complete nor was the exothermic reaction involv- 

 ing the phosphorylation completely understood. So at that time the calculation 

 of Hill and his co-workers did not lead to the final conclusion that the energy 

 as measured by heat was completely liberated from ATP. They, therefore, 

 were suspicious of other pathways. Now, however, with our better knowledge 

 of the various free energy methods and so on, you can recalculate the results 

 and still come out with a value that is comparable; that is, a value measured 

 as heat was completely explainable in terms of the energy — I mean, of the 

 heat that could be generated from the total amount of ATP present. In other 

 words, we concluded, from such a rough calculation, that there was no third 

 pathway; there was no third source of energy. If you take this conclusion as 

 a starting point, since the muscle was capable of maintaining its normal elec- 

 trical and other properties in doing mechanical work, among the two sources 

 of energy, ATP and creatine phosphate, there must be one that is completely 

 responsible for this performance. Of course, it goes back to the ATP problem 

 that Dr. Grenell has just brought up. 



Dr. McElroy: Dr. Grenell and I agree perfectly that the narcotics are 

 probably depressing the phosphate turnover. As a matter of fact we have done 

 quite a bit of work on the mitochondria in the brain to show that we can get 

 uncoupling with the concentration of compounds that he has used to show an 

 increase in the ATP concentration in the intact animal. So one is led to the 

 conclusion that the narcotic must be depressing utilization of the ATP through 

 some unknown reaction and at the same time depressing the rate of its forma- 



