DISTAL URINARY ACIDIFICATION FROM SMITH,HOMER TO THE PRESENT

Since Smith's time, the essential role of collecting duct intercalated cells in controlling net acid excretion has been recognized. Rather t han employing an H+-exchange mechanism, intercalated cells have V-ATPa se on the plasma membrane and in plasmalemma-associated tubulovesicles , which functions in the bicarbonate reabsorption, regeneration, and b icarbonate secretion required for acid-base homeostasis. Several disti nct mechanisms participate in regulating V-ATPase-driven H+ secretion in different cell types: (1) Renal epithelial cells have the capacity to express different structural forms of V-ATPase that have intrinsic differences in their enzymatic properties. 2) The kidney produces cyto solic regulatory proteins, capable of interacting directly with the V- ATPase, that may modify its activity. V-ATPases in different cell type s may differ in the degree to which their activity is affected by regu latory factors, as a result of variations in V-ATPase structure. (3) I n the alpha intercalated cell, the number of active V-ATPases on the l uminal membrane is controlled in vivo by membrane vesicle-mediated tra ffic that may require unidentified mediators. In the beta intercalated cell, the number of active V-ATPases on the basolateral membrane may be controlled by regulated assembly and disassembly, responding direct ly to extracellular pH.