940 7. MERCURIALS 



the binding might be through SH groups but, as Gergely et al. (1959) point- 

 ed out, it only indicates that SH groups are in the vicinity of the binding 

 groups. The myosin SH groups concerned with the binding of actin react 

 with mercurials more readily than the SH groups upon which ATPase ac- 

 tivity depends (Fig. 7-22) (Barany, 1959). However, MM presents an ex- 

 ception, in that it inhibits ATPase and actomyosin formation in a parallel 

 fashion (Barany and Barany, 1959 a), possibly indicating that the size 

 of the group on the mercurial is important. G-actin is more reactive than 

 F-actin, due perhaps to shielding of the SH groups in the polymerized form. 

 G-actin cannot polymerize unless ATP is present and, since mercurials re- 

 lease ATP from actin, the possibility of the effect on the G-actin ±^ F-actin 

 transformation being due to an interference with ATP binding was examin- 

 ed, but most mercurials were found to cause a rapid loss of polymerizability 

 without appreciable loss of ATP (Drabikowski and Gergely, 1963). When 

 the ATP is finally lost, the actin has been changed irreversibly, and there 

 is further evidence from optical rotation that structural changes are pro- 

 duced (Tonomura and Yoshimura, 1962). Katz and Mommaerts (1962) con- 

 sider the six SH groups of G-actin to fall into three categories: two rapidly 

 reacting, two intermediately reacting, and two slowly reacting, only the 

 last two being necessary for polymerization. It is interesting that the SH 

 groups of G-actin are made more reactive to p-MB by Mg++ and less reac- 

 tive by Ca++ (Katz, 1963). It was postulated that Mg++ brings about an 

 open configuration whereas Ca++ tends to produce a closed configuration, 

 the SH group being in a crevice. 



The effects of the mercurials on extracted muscle proteins are certainly 

 interesting and often obtained at low concentrations, but there is at pres- 

 ent essentially no way of determining if they are at all responsible for any 

 of the changes observed in intact muscle. It would be particularly important 

 to know if rigor is related to any of the actions on actomyosin, but actually 

 most of the actions described above could not very well explain why a 

 muscle goes into contracture. The mechanisms by which mercurials alter 

 muscle function are thus obscure, but it is not unlikely that the earliest 

 effects are on the permeability and transport systems in the membrane. 

 More information will be provided in the following section in which the 

 effects of the mercurials on cardiac muscle will be discussed. 



Heart 



The detrimental effects of the mercurials on the heart have long been 

 recognized and many cases of clinical deaths from intravenous injections 

 of mercurial diuretics have been reported. It is generally agreed that death 

 is attributable to the direct action on the heart during temporary high 

 plasma concentrations of the mercurials, whereas at the usual low concen- 

 trations required for diuresis there are no detectable cardiac effects. The 



