ABRAHAM M. SHANES 171 



nisms in giant axons for sodium and potassium which do not contribute directly 

 toE. 



In the presence of appreciable active transport of potassium as well as of 

 sodium, it is clearly as erroneous to use potassium influx as sodium outflux data 

 as a test for the applicability of equations derived for passive systems when 

 metabolism has not been completely inhibited. Heat measurements, such as 

 developed by Hill and his associates (11), are probably the best available 

 criterion for determining the conditions which can best achieve maximal 

 cessation of active transfer. In the case of frog nerve, anoxia combined with 

 iodoacetate poisoning appear to be satisfactory (11). Once such conditions have 

 been established, valid comparisons with hypothetical relationships are possible 

 and will provide a useful means of examining the nature of the 'passive' passage 

 of sodium and potassium through the cell boundary, about which little is 

 actually known at present. 



The action of certain drugs on ion movement, evident after the obscuring 

 effect of active transport has been reduced (44, 45), also offers promise of 

 providing information concerning the properties of the cell boundary as it 

 affects passive ion transfer. Moreover, the modifications in ion movement offer 

 a basis for the interpretation of the action of these drugs. Thus, the reduced 

 interchange of sodium and potassium in a typical 'stabilizing' anesthetic, like 

 cocaine, shown in table i, may be due either to a decreased influx of sodium, 

 decreased outflux of potassium, or both. Conversely, the action of veratrine 

 may be related to an increased penetrability of sodium. In the light of these 

 findings, the dependence of impulse initiation and production on sodium- 

 potassium exchange (20, 25) provides an obvious basis to account for the action 

 of these agents on transient bioelectrical phenomena in nerve. 



NERVE ACTIVITY AND ION TRANSFER 



In addition to fulfilling the poorly understood requirement of most cells for 

 an internal ionic environment differing from the external, the high potassium 

 and low sodium contents of the axoplasm relative to those of the medium 

 represent potential energy expendable for action potential production. The 

 negligible cellular work involved in impulse production was recognized by Hill 

 and his associates from the small initial heat (11). This is verified by the con- 

 tinued appearance of action potentials when the extra oxygen consumption 

 associated with activity is suppressed (3, 8) or when the polarized state, and 

 probably ion distribution (16, 44), are maintained by anodal polarization in 

 the presence of many different metabolic inhibitors (16, 34). It has also been 

 demonstrated in giant axons for the increased fluxes of activity; thus, such 

 ionic transfer is decreased only slightly by inhibitors which suppress active 

 transport (22). 



