l68 ELECTROLYTES IN BIOLOGICAL SYSTEMS 



poration over that of sodium; Ling (^7,) has discussed the possibilities for 

 muscle, where his findings indicate no need for work by the cells. This view is 

 tantamount to ion 'binding', which has been demonstrated in other systems 

 (6, 37). On this basis the ion content must be corrected for binding before 

 insertion in equation i ox 2. Evidence for the absence of such binding in giant 

 axons is the large percentage of radiopotassium exchange obtained within the 

 axon, and on the migration of this radioisotope in the axon, by diffusion and in 

 the electric field, with velocities comparable to that of the free ion (24). How- 

 ever, binding can occur which permits ionic exchange (30); a sufficiently 

 rapid exchangeability of this type would permit observations such as described 

 above in the presence of bound potassium. Moreover, the resting leakage of the 

 invertebrate fibers may reflect the breakdown of binding processes; from this 

 standpoint, data on the completeness of exchange in vivo are desirable. In vivo 

 experiments with rabbits indicate incomplete exchange, while in frog it may be 

 complete (14). 



h) Energy release may preserve the selective permeability of the cell surface. 



c) Metabolism may generate a potential difference across the cell boundary 

 which in turn causes ionic differences. Ussing (57) has presented impressive 

 evidence for frog skin that the transport of sodium may be directly responsible 

 for the decrease in potential on the outside, from which it is removed, relative 

 to the inside, where it accumulates; this, in turn, is associated with movement 

 by others ions in accord with equation 2 to maintain electroneutrality of the 

 bulk solutions. 



d) Metabolic reactions may operate directly at the cell surface to extrude 

 sodium and take up potassium without necessarily contributing directly to the 

 potential difference. An example of this is the model described by Osterhout 

 (36) in which the bubbling of CO2 in an 'intracellular' phase bounded by a 

 barrier more permeable to cations leads to H-K exchange and to a potential 

 difference dependent on the actual accumulation of potassium rather than on 

 the diffusion rates of the ions. In this instance the equilibrium expression for 

 2 appears to be obeyed although 'active transport' actually occurs. 



Probably the most potent tool available for discrimination between these 

 possibilities is the radioisotope. Its similarity in behavior to the normal con- 

 stituent permits the investigator to introduce a minute quantity of 'labeled' 

 ion into the fibers to serve as a measure of the rate of exit, the outflux, or into 

 the medium as a measure of the rate of entry, the influx. Under steady state 

 or equilibrium conditions, i.e. when the ion content of the fibers is constant, 

 influx and outflux are equal and the net flux — the difference in fluxes — is zero. 

 When the ion content changes as a result of experimental conditions, influx 

 and outflux will differ, and the labeling technique permits an evaluation of the 

 extent to which each flux has been affected. 



Flux measurements in nerve have been restricted largely to metabolizing 



