MITOCHONDRIA, CELLS. AND TISSUES 



585 



of the inhibition might indicate an initial reaction with the membrane lead- 

 ing to a breakdown of the barrier, in which case the curve in Fig. 12-28 

 would record the rate of reaction with the glycolytic enzymes. 



The action of iodoacetate on nerve axons is definitely limited by a slow 

 rate of penetration into the cells. At a concentration of 1.4 mM iodoace- 

 tate causes a slow fall in the respiration over 6 h, while concentrations 

 as high as 50-70 mM have little effect within an hour (Chang and Gerard, 

 1933). If the nerve sheath was split, the inhibition occurred more rapidly, 

 proving directly that a permeability barrier was present, but even then 

 the rate of inhibition was not very rapid so that some delay resulted 

 from the intracellular reactions also. Isolated brain behaves similarly and 

 exhibits a latent period that is inversely proportional to a low power of the 

 iodoacetate concentration, as shown in rat cortex slices by Fuhrman and 

 Field (1943). Tlie tabulation below has been assembled from their curves. 



Actually the latent period is somewhat shorter for glycolysis than for res- 

 piration, which might be expected on the basis that the respiratory depres- 

 sion follows secondarily to the glycolytic inhibition. When the brain tissue 

 was made into a cell-free brei, the latent period was not reduced; this sur- 

 prising observation would indicate the unimportance of penetration in 

 determining the rate of inhibition, but certainly such long latent periods in 

 cell-free preparations are contrary to what has been observed in muscle 

 and other tissue extracts. When the pH was lowered from 7.3 to 5.8, the 

 latent period was shortened and Fuhrman and Field felt this might impli- 

 cate permeability factors, but actually all that is done by lowering the 

 pH is to increase the concentration of the permeant undissociated acid and 

 either penetration or reaction with enzymes would be expected to be in- 

 creased. 



Rate studies of metabolic inhibition have occasionally been used in con- 

 junction with measurements of functional depression in order to determine 



