448 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1957 



around the regulatory mechanisms, especially of the higher animals, 

 developed for the maintenance of an optimum distribution in the body. 



The high potassium content of the parenchymatous cells as opposed 

 to the higher sodium chloride content of the blood serum has been 

 recognized at least since von Liebig's time. Soon thereafter, many 

 studies were conducted which gradually led to the recognition that, 

 in disease, the low sodium chloride content of the cell increases while 

 the potassium level decreases. Speculation as to how the body can 

 maintain the high concentration gradients within the distance of a 

 few microns between the surface of the cell and the blood plasma origi- 

 nally involved the idea of the specific permeability of cell membranes. 

 It was held that the cell membrane is specifically permeable to potas- 

 sium salts and almost impermeable to sodium chloride under normal 

 conditions and that this is disturbed in disease. 



Some investigators recognized the weaknesses of these hypotheses 

 at an early date. Keller, in particular, attacked the idea that the 

 separation of the minerals was due to the function of an "inert" mem- 

 brane rather than to the discriminatory power of the whole living 

 cell. He tried to replace this static view with his electrostatic theory, 

 the study of which is still rewarding even after 50 years. Neverthe- 

 less, the permeability theory was accepted by most biologists until 

 isotope studies proved that the cell membrane is equally permeable 

 to both potassium and sodium salts and that the low sodium chloride 

 content of the cell is due to its rapid expulsion from the cell. This 

 mechanism is now often referred to as the "sodium pump," a term 

 which might well be improved. Although these studies prove that 

 the removal of sodium chloride from the cell is a dynamic process 

 the disturbance of which leads to the accumulation of sodium chlo- 

 ride within the cell, and although many modern physiologists have 

 demonstrated the weaknesses of the membrane theory, some investi- 

 gators are not as yet ready to give it up entirely. 



The modern concept of competitive antagonisms within enzyme 

 systems, which gradually evolved from studies on minerals, has proved 

 a useful tool for the understanding of some functions of sodium and 

 potassium salts. In practically all biochemical and pharmacological 

 studies, it has been shown that sodium and potassum have opposite 

 functions. For example, potassium salts favor diuresis ; sodium salts 

 do the opposite. Many more examples have been cited. Lately, 

 some evidence has been put forth that this antagonism is particularly 

 important in regard to the action of chloride, the biological effect of 

 which depends upon whether it is accompanied by sodium or 

 potassium. 



In studies concerned with the question of why sodium chloride is 

 essential for the living cell, tenable ideas are sketchy. It seems im- 



