900 7. MERCURIALS 



ecular stress" brought about by the formation of S — Hg — S bridges in the 

 membrane; when this stress reaches a critical level, the membrane disinte- 

 grates and cellular components are released (Rothstein, 1959). Little con- 

 sideration is given to the possible effects of Hg++ on the active transport 

 mechanisms by which K+ is accumulated and emphasis is placed on the 

 structural changes occurring in the membrane. Most of the studies on K+ 

 loss from tissues have been interpreted in terms of an inhibition of active 

 transport (page 907), and it seems that this would be the more direct and 

 logical explanation. It should also be pointed out that, as in all studies of 

 the effects of substances on transmembrane fluxes, it is very difiicult to 

 distinguish between actions on the membrane and within the cells, and 

 that therefore these results in themselves cannot be taken as evidence for 

 a direct or specific membrane effect. 



Erythrocyte Permeability and Hemolysis 



Organic mercurials increase erythrocyte fragility and promote hemolysis, 

 often at quite low concentrations, but the effects of Hg++ are more complex, 

 hemolysis being either favored or inhibited depending on the conditions, of 

 which the concentration of Hg++ and the type of hemolysis are the most 

 important. If hemolysis in isotonic glycerol is studied, Hg++ can markedly 

 delay the hemolysis. Human erythrocytes hemolyze rapidly in isotonic gly- 

 cerol at pH 7.2; as the concentration of Hg++ is increased, inhibition is first 

 observed at 0.025 mM and very strong inhibition at 0.05 mM (Wilbrandt, 

 1941). This was interpreted as an inhibition of glycerol entry into the cells 

 by Hg++. On the other hand, if hypotonic hemolysis of human erythrocytes 

 is examined (i.e., hemolysis in Tyrode solution diluted to varying degrees), 

 Hg++ can either accelerate or slow hemolysis (Fig. 7-39) (Jung, 1947). In 

 normal or weakly diluted medium, Hg++ favors hemolysis, but at low con- 

 centration it suppresses hemolysis in markedly hypotonic media. Jung be- 

 lieved that the resistance to osmotic effects is mediated through a denatur- 

 ation of the membrane. Arbuthnott (1962) has recently confirmed the dual 

 action of Hg++, hemolysis of rabbit erythrocytes being promoted by low 

 concentrations and inhibited by concentrations around 1 mM. Organic mer- 

 curials {p-MB, ethyl-Hg+, and thimerosal), however, are only lytic, even 

 at high concentrations. Arbuthnott related this to the number of charges 

 on the mercurials, although it is more likely a matter of the ability of 

 Hg+"'" to form S — Hg — S bridges which increase the stability of the mem- 

 brane. These effects of the mercurials on erythrocytes may or may not de- 

 pend on metabolic inhibition, but they are important nexvertheless in un- 

 derstanding the actions of the mercurials on cell membranes in general, 

 since the mammalian erythrocyte presents an especially simple system for 

 investigation and has been well studied. 



Hg++ appears to have greater lytic potency than the organic mercurials. 



