Abstract
The intracellular pH in animal cells is generally maintained at a higher level than would be expected if H+ were passively distributed across the plasma membrane1. In a wide variety of cells including sea urchin eggs2, skeletal muscle3, renal and intestinal epithelial cells4–6, and neuroblastoma cells7, 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+ exchanger4,5 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 N+–H+ exchangers, mediates electroneutral cation exchange4,5, is sensitive to inhibition by the diuretic drug amiloride5,8, 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 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.
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Aronson, P., Nee, J. & Suhm, M. Modifier role of internal H+ in activating the Na+–H+ exchanger in renal microvillus membrane vesicles. Nature 299, 161–163 (1982). https://doi.org/10.1038/299161a0
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DOI: https://doi.org/10.1038/299161a0
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