GENERAL COMMENTS 157 



sequence of events is fully in accord with the view that in brain, as 

 in muscle, phosphocreatine serves largely to maintain normal 

 levels of adenosine triphosphate. This view is strengthened by the 

 observations that, in cerebral dispersions, the only reaction so far 

 described for phosphocreatine is the phosphorylation of adenosine 

 diphosphate to the triphosphate. In this respect, changes in the 

 labile phosphates of cerebral tissue are similar to those found in 

 muscle during contraction and rest but the analogy cannot be 

 carried too far. In muscle the energy released appears largely as 

 contractile work, but in the brain where contractile mechanisms 

 are mainly absent the energy must be used for other purposes of 

 which that of maintaining a continuous balance in the ionic shifts 

 vv^hich give rise to fluctuating potentials detected by the electro- 

 encephalogram, probably requires the largest portion. Ideas 

 expressing ways in which metabolically derived energy may be 

 used for such a process in nervous tissue have been summarized in 

 Fig. 14. In this sequence, the energy-rich phosphates of adenosine 

 and creatine are linked metabolically with guanosine nucleotides 

 and phosphoprotein, which in turn is considered to be linked to the 

 mechanism transporting ions from one surface of a membrane to 

 the other. When this mechanism is altered, for example by an 

 externally applied potential, an increased rate of metabolism and 

 turnover of phosphate occurs as the system endeavours to reattain 

 equilibrium. The existence of a chain of reactions such as this 

 affords a possible explanation of the effects in vivo of partial anoxia 

 abolishing spontaneous cortical potentials while leaving levels of 

 phosphocreatine unaffected. 



A scheme somewhat similar to that of Fig. 14 has been discussed 

 by Richter (Richter and Crossland, 1949; Richter, 1952) in which 

 the breakdown of phosphocreatine is linked, via adenosine triphos- 

 phate, with the maintenance of adequate levels of acetylcholine. 

 This type of sequence undoubtedly occurs, but it is unlikely that 

 it accounts for more than a small part of the energy available. The 

 greatest rate of breakdown of acetylcholine observed m vivo is 

 some 5 jLtmoles/g hr-^ and the rate of synthesis is less than this, 

 though rates of up to 70 /umoles/g hr-^ have been obtained with 

 preparations from the head of the blowfly (Hebb, 1957). These 

 rates are to be compared with the rates of breakdown of phos- 

 phocreatine. 



Although the mechanism linking the energy of the phosphate 



