CLUES FROM ASSOCIATED EVENTS 



interesting one. A nonmitochondrial phosphoprotein of liver slices 

 shows a phosphorus turnover sensitive to the presence of sodium 

 ion and of strophanthin (Ahmed and Judah, 1962). 



Another important association of alkali metal transport with a 

 chemical event is the correlation with an ATPase activity, developed 

 by Dunham and Glvnn, by Skou, and by Post and his associates. 

 Skou (1957; 1960) discovered an ATPase of crab nerve that is 

 particularly sensitive to Na+ and Mg ++ . Dunham (1957) observed 

 that 10~ 6 M strophanthidin diminished strongly the cleavage of 

 ATP in the red blood cell, in association with an inhibition of 

 potassium-ion influx (Schatzmann, 1953). Glynn (1957b) showed 

 that scillarin A at very low levels acts as a competitive inhibitor of 

 potassium-ion entry. Post observed that red blood cell stroma 

 reached its maximal ATPase activity only when the sodium and 

 potassium were set at certain concentrations. When both ions were 

 set at ion levels permitting half-maximal alkali metal transport, the 

 ATPase activity also became half-maximal. Ouabain produces a 

 half-maximal inhibition of the ATPase at 10 ~ 7 M, also a half-maxi- 

 mal inhibition of cation transport (Post, 1959; Dunham and Glynn, 

 1960). This enzymatic ATP-splitting activity is associated with 

 portions of the stroma that are not solubilized by deoxycholate 

 (Post et al, 1960). 



These experiments appear to identify the ATPase activity with 

 the alkali metal transport process. The uphill transport of a number 

 of solutes other than the alkali metal ions is also inhibited by very 

 low levels of the cardiac glycosides and their derivatives. These 

 include monosaccharides (Csaky et al., 1961), halide ions (Wolff 

 and Maurey, 1958), and serotonin (Weissbach et al., 1960). Such 

 results suggest that the relationship of ATPase action to uphill 

 transport may be general. 



Experiments by Caldwell (1959; 1960) and Caldwell and asso- 

 ciates (1960) have, in the meantime, provided what is perhaps de- 

 cisive evidence that high-energy phosphate compounds (perhaps 

 ATP specifically) are the carriers of energy from the mitochondrion 

 to the alkali metal transport apparatus. 



These investigators injected ATP and other high-energy phos- 

 phorus compounds into the squid axon by use of a fine cannula in- 

 serted along the middle of the fiber. A section of axon had first been 

 labeled with ionic Na 22 and then poisoned with cyanide; in this 



8i 



