PENETRATION OF ARSENICALS INTO CELLS 699 



51% by 1 mM arsenite, whereas the respiration of an extract is inhibited 

 only 7%. 



Arsenite depresses the action potential of frog sciatic nerve after a lag 

 period of 1-3 hr; it was thought this might be related to impenetrability 

 of the surrounding membranes, but splitting the neural sheath has little 

 effect on this (Schmitt et al., 1934). Furthermore, the action on the respira- 

 tion is quite rapid, indicating adequate penetration. The rate of penetration 

 may depend on the functional activity of a tissue, since arsenite is absorbed 

 faster by stimulated brain in rabbits; if one sciatic nerve is stimulated there 

 is more arsenite picked up by the contralateral side of the brain (Pigalev, 

 1940). The uptake of arsenite also increases with the fermentation activity 

 in yeast (Diemair and Schiilke, 1941). In experiments of this type one 

 cannot be certain whether it is a matter of increased permeability or more 

 binding sites. 



The marine alga Valonia has often been used in permeability studies be- 

 cause it is possible to determine the concentrations of material in the proto- 

 plasm and the cell vacuolar fluid, so that surface binding can be eliminated. 

 Brooks (1923, 1925) studied the entrance of arsenite into Valonia cells 

 and found almost all taken up to be in the protoplasm, presumably because 

 of binding to proteins. The uptake is minimal at an external pH of around 7. 

 The effects of pH on penetration were discussed in terms of the ionization 

 of arsenious acid, but there is obviously no simple relation between uptake 

 and the concentration of the un-ionized form, and the author concluded 

 that this is not the major factor in determining the rate of entrance. The 

 uptake of arsenite was actually rather slow in these experiments and per- 

 haps one might question whether permeability is measured under these 

 circumstances. Most of the arsenite in the protoplasm must be bound and 

 hence the uptake may be indicative only of the rate at which binding 

 sites become available, particularly since 2 mM arsenite damages the cells. 

 Although dead cells take up arsenite more rapidly than live ones, it is 

 still a slow process. Ricks and Hoskins (1948) studied the effects of pH 

 on the uptake of arsenite by flesh fly larvae and found that penetration 

 decreases with rise in the pH (see accompanying tabulation). The less 



uptake at the high pH's could well be due to ionization of arsenious acid 



