896 7. MEKCURIALS 



in the total membrane, but it seems very unlikely that it could accommo- 

 date all the Hg++ taken up at the higher concentrations, especially if pene- 

 tration deep into the tissue does not occur. 



The uptake data by themselves could be explained in a variety of ways. 

 Binding to proteins often shows different phases due to the different reac- 

 tivities of the various types of SH group, and in cellular systems one must 

 perhaps also consider ligands other than SH groups. But how can one inter- 

 pret the results on glucose utilization and respiration, especially as they 

 seem to be correlated in time with the Hg++ uptake phases? Particularly, 

 why is there such a long lag period before respiration is depressed? It may 

 be noted that a lag period is not always observed in other tissues or cell 

 suspensions. One possibility which cannot be ignored is that the Hg++ en- 

 ters the cells early but is initiaUy and preferentially bound to SH groups 

 not involved with respiration. In muscle cells this might be more evident 

 than in other tissues because of the large amounts of actin and myosin, 

 each of which possesses numerous SH groups; only when these groups be- 

 come saturated with Hg++ would effects on the oxidation enzymes be ob- 

 served. It is unfortunate that the effects on muscle contraction were not 

 determined, since if this explanation is valid, contractile activity should 

 be reduced during the fast phase of uptake. In this case the fast phase 

 would refer to the binding to membrane and actomyosin (and any other 

 reactive ligands), the membrane contributing only slightly. The kinetics 

 of the effects of mercurials on diaphragm contraction have apparently not 

 been studied, but one notes that the diaphragms exposed to 1 mM p-MB 

 for 30 min by Kono and Colowick (1961) were stated to be in contracture. 

 On the other hand, the results obtained with rat atria exposed to 0.05 mM 

 p-MB indicate that no effect on the contractile amplitude occurs during the 

 initial 22 min, although effects on the membrane are evident (decrease in 

 magnitude and duration of the action potential), and that depression of the 

 contraction proceeds subsequently (Webb and Hollander, 1959). These re- 

 sults on atria thus would fit into the theory of Rothstein. However, it must 

 be remembered that in obtaining transmembrane potentials one examines 

 only the outermost cells, and that contractile amplitude involves the entire 

 tissue; for this reason one would expect a delay in contractile response. A 

 decision cannot be made until direct experiments on respiratory and con- 

 tractile response are made in diaphragms. It must be emphasized that any 

 modification of the concepts of Rothstein suggested here are not necessarily 

 applicable to other heavy metal ions or other cells (especially yeast), but 

 relate to mercurials only. 



Another factor which must be considered in tissue uptake studies with 

 the mercurials is the possibility of damage to the external layers, mani- 

 fested by increased permeability and exposure of reactive SH groups, espe- 

 cially with the higher concentrations often used. The high degree of bind- 



