EFFECTS ON TISSUE FUNCTIONS 937 



transporting pores by reacting with SH groups on the walls, or interfere 

 with the open-closed transition postulated to occur in the membrane by 

 Kavanau (1963). White et al. (1961) have provided the only direct evidence 

 that mercurials increase the permeability of the proximal tubule cells to 

 Na+. They infused Na^' into the renal artery during mannitol diuresis and 

 found the Na+ flux to be increased by meralluride at diuretic doses. It was 

 thus concluded that the net resorption of Na+ is decreased because of the 

 augmented backward leak. 



EFFECTS ON TISSUE FUNCTIONS 



Surprisingly few thorough or quantitative investigations of the effects of 

 mercurials on tissue function have been made, especially considering the 

 long-known toxic and therapeutic actions of these substances, and most of 

 them are on the heart. Since in essentially no case have functional and 

 metabolic disturbances been correlated, most of the results will be treated 

 cursorily and presented principally to point out some fields in which inter- 

 esting work may be done. There is great need for the study of the metabolic 

 changes produced in tissues isolated from animals treated with mercurials, 

 since only in this way can one be certain that the effects observed are re- 

 lated to the in vivo interference with function. This has been done with 

 the kidney but is notably absent with other tissues. Much of the in vitro 

 work with mercurials has been done with relatively high concentrations 

 (around 1 mM or higher) so that it is impossible to determine if the 

 results are applicable to the effects seen in the whole animal. Indeed, 

 studies of the simultaneous changes in fuction and metabolism under 

 any conditions are very rare. 



Skeletal Muscle 



Resting rat diaphragm treated with 1-2 niM mersalyl soon exhibits fibril- 

 latory twitches accompanied by rapid small (1 mv) variations of the mem- 

 brane potential, which persist for several minutes, followed by a rise in 

 the resting tension during the next 10 min, and finally by a further slowly 

 developing irreversible contracture and loss of excitability (Kuschinsky et 

 al., 1953). Stimulation during the early action of mersalyl produces a nor- 

 mal contractile tension but there is a marked retardation of relaxation, 

 the duration of contraction increasing 5- to 10-fold. Hg++, on the other 

 hand, causes only the slow contracture and loss of excitability. Decame- 

 thonium and curare abolish the fibrillation due to mersalyl, indicating that 

 the action of the mercurial is on the end-plate. Furthermore, chronically 

 denervated muscle does not show mersalyl fibrillation. Inasmuch as physo- 

 stigmine and neostigmine cause a similar fibrillation, and since mersalyl 



