D. C. TOSTESON I2g 



The rate of transport of a cation which reacts with a component of the red 

 cell membrane may be expected to be competitively inhibited by other ions of 

 similar physico-chemical properties. Thus, the demonstration of competitive 

 kinetics is consistent with, but does not prove the existence of transport by 

 chemical reaction. On the other hand, absence of competitive relations does 

 not rule out transport by chemical reaction, since the membrane reactant may 

 have a very specific affinity for only one ion. 



Relation of Transport Process to Metabolism of the Cell. If an ion reacts 

 with one or more organic compounds in traversing the cell membrane, dis- 

 turbances in the metabolism of the organic compound will affect ion transport. 

 Since the cell can be represented as an organized system of organic chemical 

 reactions in the steady state, disturbances in one part of the system may be 

 expected to affect all of the organic compounds in the cell. Therefore, demon- 

 stration that changes in the rate and pathway of degradation of organic sub- 

 strates by the cell alters ion transport is certainly consistent with the idea 

 that the ion reacts with one or more organic intermediates. However, normal 

 cell metabolism may be required in order to maintain constant the diffusion 

 characteristics of the cell surface. In order to show that metabolism afifects ion 

 transport via specific chemical reactions between ion and metabolite, it is 

 necessary to show that altered ion movement in cells in which metabolism has 

 been modified experimentally cannot be attributed to diffusion. 



Several experimental procedures are useful in demonstrating the relation 

 between ion transport and cell metabolism. These include the effect of: /) vary- 

 ing gas composition of the medium; 2) different substrates; j) metabolic 

 inhibitors. 



It should be noted that all of the criteria for detection of specific chemical 

 reactions involved in ion transport outlined above are essentially indirect. 

 Conclusive proof of the existence of such reactions requires identification of 

 the membrane reactant. 



ANALYSIS or EXPERIMENTAL RESULTS 



Human Red Cells 



Normal. Before reviewing in detail the experimental evidence now available 

 regarding K and Xa transport in human red cells, we will first brietly consider 

 the structure and ionic composition of the cell. The human red cell is a bi- 

 concave disk about 8.5 microns in diameter and 2.4 microns thick (84). We 

 will be concerned mainly with the molecular anatomy of the plasma membrane 

 of the cell. Although estimates of the thickness of this membrane vary widely 

 (41, 63), it is probable that the layer of importance for permeability considera- 

 tions is from 6o to 100 A thick. 



Recent information (41, 64) has amplified the view of Parpart and Ballen- 

 tine (75) that the red cell membrane is a mosaic structure containing both 



