FACTORS AFFECTING METABOLISM in vitro 111 



When slices of cerebral cortex are suitably stimulated by electrical 

 impulses (p. 113) the quantities of inorganic phosphate and phos- 

 phocreatine change in a reciprocal manner. By adjusting the 

 intensity of the stimulus the extent of this change can be regulated. 

 Comparison of the levels of these phosphates with the oxygen 

 uptake of the intact slice under similar conditions (Fig. 11) then 

 reveals a relationship of the type noted above in disintegrated 

 preparations. Thus, when levels of phosphocreatine and inorganic 

 phosphate had changed by about 20% oxygen uptake was in- 

 creased by 40% ; when phosphate levels changed by 40% oxygen 

 uptake had increased by 75%.. Although these results are a 

 synthesis of two sets of data the use of identical conditions of 

 stimulation permits a comparison in this manner. The results in 

 Fig. 11 thus complement the deductions of Mcllwain. However 

 it will be noted that the increase in concentration of inorganic 

 phosphate from 2-3-3-2/xmoles phosphorus/g wet wt. represents 

 only one-fifth of the increase needed to obtain the doubling in the 

 rate of oxygen uptake which is normally obtained if the systems 

 involved are similar to those studied in dispersions. Many 

 phosphate dependent steps are involved in the oxidation of glucose 

 and an increase of 20% in the levels of inorganic phosphate may 

 produce a series of small but additive increases in their rates of 

 reaction. Alternatively the overall change in concentration may 

 represent a larger change taking place at localized areas for it is 

 unlikely that inorganic phosphate is distributed evenly throughout 

 the tissue. 



The Effects of Electrical Stimulus 



A major problem in the biochemistry of nervous tissue is the 

 manner in which energy-yielding processes are connected to those 

 requiring energy. In Chapter 2 an account was given of the way 

 in which such relationships had been studied in vivo. However, the 

 complexity of the in vivo system imposes severe limitations to 

 experimentation and a major advance in the examination of these 

 relationships has only become possible with the discovery that 

 applied electrical stimulus could induce changes in tissue slices 

 in vitro similar to those occurring in the whole brain in vivo. It was 

 shown (Mcllwain, 1951; Mcllwain et al., 1951) that the applica- 

 tion of alternating electrical impulses of a defined type to slices of 

 cerebral cortex metabolizing glucose in a suitable oxygenated 



