134 ELECTROLYTES IN BIOLOGICAL SYSTEMS 



The deviation of the [Na],,, = o intercept from zero could be construed as 

 evidence against the assumption that the whole of the Na influx is by diffusion. 

 However, this deviation may be referable to the substitution of sucrose- 

 melezitose for NaCl in the experiments in which [Na]m was reduced. This pro- 

 cedure would lower and eventually reverse the value of [Cl],n/[Cl]c , thus alter- 

 ing the electrical potential across the membrane in such a way as to reduce 

 the 'kN.i at low values of [Na],„ . 



Comparable studies of Na outflux as a function of [Najc have not been re- 

 ported due to the experimental difficulty involved in altering the ionic compo- 

 sition of the cell. The problem of expressing sodium outflux as a function of 

 [Na]c in normal human red cells is particularly thorny because about 20% of 

 the cell Na appears to exchange much more slowly than the remaining 80%, 

 both in vitro (95, 100), and in vivo (25). The chemical explanation for this 

 finding is, at present, obscure. It has been shown that Na outflux is not af- 

 fected by variations in cell volume due to exposure to hypotonic media (36). 



Effect of temperature. The high apparent activation energies for K influx and 

 outflux (12,000-15,000 cal/mole), Na influx (20,000 cal/mole) and outflux 

 (15,000 cal/mole) (87, 94, 100), are consistent with transport via chemical 

 reactions for all four processes. However, as pointed out in the theoretical 

 section, deductions from this temperature data with regard to mechanism of 

 transport must be extremely cautious. 



Competition between ions. The normal human red cell membrane cannot 

 distinguish between K and rubidium (53, 100). Cesium also competes with 

 these ions for entrance (53, 100, 107, no), but is only about one fifth as ef- 

 fective as Rb and K. The ratio 'kcs/'kK is about .15 while °kcs/°kK is about 

 .62 when [K]ni = 4.5 mM/1. in normal human cells (17). Thus, if the two ions 

 do compete for exit from the cell, Cs is a much more effective competitor than 

 it is in the influx process. Neither lithium nor sodium appear to compete with 

 K for entrance into the cell. On the other hand, lithium competes on almost 

 even terms with Na for influx (100). K, Rb, and Cs do not affect Na influx. 



It is found that the ratio 'kos/'kR increases when [K],n increases in both 

 normal (17) and abnormal human cells (106, 109). If the data on normal cells 

 are analyzed assuming that the competition ratio for a chemical reaction path- 

 way is invariant with concentration, and that the variation in 'kcs/'kK with 

 [K]n, is due to the presence of a diffusion pathway for which no competition 

 occurs, values for D'k and D'cs may be calculated which can be compared 

 with values obtained by flux ratio analysis. Results of such a calculation by 

 this concentration curve-competition method for normal human cells at 25°C 

 yield values of D'k and D'cs of .0015 and .0023 respectively. These may be 

 compared with the values D'k = .0042 and D'^s = -0037 by the flux ratio 

 analysis of the same data. 



