194 



ELECTROLYTES IN BIOLOGICAL SYSTEMS 



the solution bathing the mucosal surface of the isolated frog mucosa partially 

 inhibits the spontaneous potential and short-circuit current. The lower secre- 

 tory to nutrient chloride flux observed with bicarbonate present in the secretory 

 solution has also been noted in the absence of Diamox. The changes noted in 

 table 2 are not attributable to the passage of time as the sequence of the steps 

 was reversed in alternate experiments. The reversal of Diamox inhibition by 

 bicarbonate suggests that the Diamox inhibition is an inhibition of carbonic 

 anhydrase. 



The role of carbonic anhydrase in active transport involving H+ secretion 

 is much more obscure than suggested by diagrams so frequently encountered 

 which show the secreted H+ ion as being derived from carbonic acid. Davies 

 (24, 26) has developed the most explicit explanation for the role of carbonic 



Table 2. Carbonic anhydrase inhibitor and carbonic acid system; meq cm"^ hr.~^ 



Effect of 'Diamox' ( ^ 6063) on chloride fluxes and mucosal short-circuit current (I) and 

 the reversal of Diamox inhibition by bicarbonate. Chloride flux N -^ S is the nutrient to 

 secretory flux, flux S ^ N is the secretory to nutrient flux, and the difference ACI is the net 

 flux. The rate of hydrogen ion secretion (H"'') has been estimated from the difference between 

 net chloride flux and mucosal short-circuit current. Short-circuited isolated mucosa, R. 

 catesbiana. 6063 (Diamox) = 10 mM/l.;C02 = 5%; HCOs" = 20 mii/l. Nutrient solution — 

 5% CO2, 20 mM/1. HCOs" saline. Secretory solution — saline. 



anhydrase in acidification. The ability of the cell to secrete H+, and even its 

 integrity, is dependent on a critical intracellular pH. Unless there were pro- 

 vision for escape of a hydroxyl equivalent from the face of the cell opposite to 

 the face across which H+ is secreted, the intracellular pH would rise due to ac- 

 cumulation of 0H~. In this explanation, successful regulation of the intra- 

 cellular pH requires catalysis of CO2 hydration by carbonic anhydrase. It is 

 assumed that CO2 moves freely between cell and environment. Within the cell 

 CO2 is swiftly hydrated, in the presence of carbonic anhydrase, to bicarbonate 

 which can then passively diffuse out of the cell, limiting accumulation of 0H~ 

 and thus maintaining a constant intracellular pn. The basis for this explanation 

 was the claim that the ability of the isolated frog mucosa to continuously secrete 

 H"*" is dependent on the presence of exogenous carbon dioxide. 



There is no doubt that if there is exogenous CO2, it will be consumed and ap- 



