Modifier role of internal H+ in activating the Na+-H+ exchanger in renal microvillus membrane vesicles.
The intracellular pH in animal cells in generally maintained at a higher level than would be expected if H+ were passively distributed across the plasma membrane. In a wide variety of cells including sea urchin eggs, skeletal muscle, renal and intestinal epithelial cells, and neuroblastoma cells, plasma membrane Na+-H+ exchangers mediate the uphill extrusion of H+ coupled to, and thus energized by, the downhill entry of Na+. Plasma membrane vesicles isolated from the luminal (microvillus, brush border) surface of renal proximal tubular cells possess a Na+-H+ exchanger that seems to be representative of the Na+-H+ exchangers found in other tissues. For example, the renal microvillus membrane Na+-H+ exchanger, like other Na+-H+ exchangers, mediates electroneutral cation exchange, is sensitive to inhibition by the diuretic drug amiloride, and has affinity for Li+ in addition to Na+ and H+ (refs 5, 9). Here we have examined the effect of internal H+ on the activity of the Na+-H+ exchanger in renal microvillus membrane vesicles. Our results suggest that internal H+, independent of its role as a substrate for exchange with external independent of its role as a substrate for exchange with external independent of its role as a substrate for exchange with external Na+, has an important modifier role as an allosteric activator of the Na+-H+ exchanger. Allosteric behaviour with respect to internal H+ is a property that would enhance the ability of plasma membrane Na+-H+ exchangers to extrude intracellular acid loads and thereby contribute to the regulation of intracellular pH.
D000494:Allosteric Regulation; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000648:ultrastructure*; D007687:Kidney Tubules, Proximal / Q000648:ultrastructure; D008871:Microvilli / Q000378:metabolism* / Q000648:ultrastructure; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D006859:Hydrogen; D012964:Sodium