D. C. TOSTESON 1 25 



of organization, and also focus attention on the most important problems which 

 have yet to be solved in the tield of cation transport across the red cell mem- 

 brane. 



We will attemj)t to formulate criteria characteristic of transport by diffusion, 

 on the one hand, and by chemical reactions with components of the cell mem- 

 brane, on the other. By diffusion, w'e mean a process for which the sole driving 

 force throughout the membrane is the electro-chemical potential gradient of 

 the transported ion. That is, 



where Mj is the tiux, A the area available for diffusion in the x direction (nor- 

 mal to the surface of the membrane), G the frictional coefficient, Cj the con- 

 centration, and /Zj the electro-chemical potential of the jth ion. Thus, we ar- 

 bitrarily define transport of the jth ion by diffusion as the case in w^hich the 

 other potential gradients (e.g. electro-chemical potentials of other components, 

 temperature, pressure) do not significantly contribute to the driving force for 

 the jth ion. In terms of irreversible thermodynamics, we assume that the 

 cross coefficients relating other potentials to the flux of the jth ion are essen- 

 tially zero in the case of diffusion. We will refer to all transport processes of the 

 jth ion which are driven by some additional forces besides its own electro- 

 chemical potential gradient as transport involving chemical interaction between 

 the transported ion and one or more carrier molecules. (By this choice of terms 

 we restrict 'additional forces' to the electro-chemical potential gradients of 

 components other than the jth ion. The elimination of temperature and pres- 

 sure gradients from consideration is somewhat arbitrary, but also justified to 

 some extent by the characteristics of the systems w'hich we will discuss. It is 

 probable that there is no appreciable pressure gradient across the red cell 

 membrane. The possibility of microtemperature gradients across the red cell 

 membrane cannot be ruled out on the basis of present evidence, but seems im- 

 probable.) We will not further refine the classification of transport processes 

 beyond these two broad categories. Several recent extensive theoretical treat- 

 ments of ion transport across complex membranes are available in the litera- 

 ture (10, 79, 105). The recent critical essay by Rosenberg (89) is particularly 

 pertinent. 



Experimental Criteria Characteristic of Transport by Diffusion and 

 Chemical Reaction 

 We now consider the experimental procedures by which transport of cations 

 across the red cell membrane may be characterized. Particular emphasis will 

 be placed on the distinction between experimental results consisent with trans- 

 port by diffusion, on the one hand, and transport by specific chemical reaction 

 on the other. 



