D. C. TOSTESON 135 



These fmdings are consistent with tlie idea that K enters the human red 

 cell largely via one or more chemical reactions for which Rb, and less effectively, 

 Cs compete. About 5% of the K intlux (when [K]„, = 5 mM/1.) may be by a 

 diffusion pathway for which Cs does not compete. Li and Na appear to com- 

 pete for a different entrance pathway which may or may not involve a chemical 

 reaction. The degree of competition between the alkali cations for outward 

 transport has not been established experimentally due to the difficulty in 

 adjusting the cellular concentrations of the ions without irreversibly altering 

 the cell. However, Xa outflux is reduced when the K concentration in the 

 medium is reduced below i mM/1. (24, 35). This fact has led Harris to propose 

 that K intlux and Na outflux are linked (34). 



Relation of cation transport to metabolism. The relation of cation transport to 

 cell metabolism has been the subject of extensive research since the demon- 

 stration that K reaccumulation and Na extrusion by cold stored human red 

 cells when incubated at 37°C depends on glycolysis (12, 38). 



a) Effect of gas composition. The transport of neither K nor Na is affected 

 by changing the gas composition of a human red cell suspension from O2 to 

 N2 (87, 100, 108). This is not surprising in view of the facts that glucose me- 

 tabolism in this cell goes almost entirely via glycolysis in O2 and No , and that 

 the glucose consumption is only slightly accelerated by anoxia (15). 



b) Effect of substrate. Glucose, mannose and fructose support the net 

 extrusion of Na and accumulation of K by human red cells which have been 

 depleted by K by cold storage in the absence of substrate (58). Galactose, 

 arabinose, pyruvate, lactate and the disaccharides are not effective in this 

 respect. Only the former three sugars will support glycolysis. Studies of the 

 effect of various substrates on the unidirectional fluxes of K and Na measured 

 with isotopes have not been reported for normal human red cells. However, 

 removal of glucose from the medium reduces K influx without appreciably 

 affecting outflux in the red cells of normal individuals (24) and of patients 

 with sickle cell anemia (109). 



c) Effect of inhibitors. Studies of the effect of metabolic inhibitors on K 

 and Na transport have been numerous since Wilbrandt's finding that sodium 

 fluoride (NaF) and sodium iodoacetate (lAA) increase the time required for 

 hemolysis of human red cells in isotonic glycerol solutions, presumably by in- 

 creasing the permeability of the cell membrane to cations (119). 



lAA inhibits the net accumulation of K and extrusion of Na by previously 

 cold stored human red cells (58). This compound in a concentration of .001 

 m/1. inhibits glycolysis, presumably by reacting with the — SH groups of triose 

 phosphate dehydrogenase (30). IAx\ inhibits K influx and Na outflux, stimulates 

 K outflux, but does not affect Na influx in normal human red cells (55) and 

 inhibits K influx without affecting outflux in sickle cell anemia red cells (109). 



