Renal intercalated cells are rather energized by a proton than a sodium pump
- 22 April 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 110 (19), 7928-7933
- https://doi.org/10.1073/pnas.1221496110
Abstract
The Na+ concentration of the intracellular milieu is very low compared with the extracellular medium. Transport of Na+ along this gradient is used to fuel secondary transport of many solutes, and thus plays a major role for most cell functions including the control of cell volume and resting membrane potential. Because of a continuous leak, Na+ has to be permanently removed from the intracellular milieu, a process that is thought to be exclusively mediated by the Na+/K+-ATPase in animal cells. Here, we show that intercalated cells of the mouse kidney are an exception to this general rule. By an approach combining two-photon imaging of isolated renal tubules, physiological studies, and genetically engineered animals, we demonstrate that inhibition of the H+ vacuolar-type ATPase (V-ATPase) caused drastic cell swelling and depolarization, and also inhibited the NaCl absorption pathway that we recently discovered in intercalated cells. In contrast, pharmacological blockade of the Na+/K+-ATPase had no effects. Basolateral NaCl exit from beta-intercalated cells was independent of the Na+/K+-ATPase but critically relied on the presence of the basolateral ion transporter anion exchanger 4. We conclude that not all animal cells critically rely on the sodium pump as the unique bioenergizer, but can be replaced by the H+ V-ATPase in renal intercalated cells. This concept is likely to apply to other animal cell types characterized by plasma membrane expression of the H+ V-ATPase.Keywords
This publication has 56 references indexed in Scilit:
- A mouse model for distal renal tubular acidosis reveals a previously unrecognized role of the V‐ATPase a4 subunit in the proximal tubuleEMBO Molecular Medicine, 2012
- Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failureProceedings of the National Academy of Sciences, 2012
- Specification of ion transport cells in theXenopuslarval skinDevelopment, 2011
- Sodium and Potassium Balance Depends on αENaC Expression in Connecting TubuleJournal of the American Society of Nephrology, 2010
- The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of miceJournal of Clinical Investigation, 2010
- Connexin 30 Deficiency Impairs Renal Tubular ATP Release and Pressure NatriuresisJournal of the American Society of Nephrology, 2009
- Electrotonic vascular signal conduction and nephron synchronizationAmerican Journal of Physiology-Renal Physiology, 2009
- Deoxycorticosterone Upregulates PDS ( Slc26a4 ) in Mouse KidneyHypertension, 2003
- The vacuolar (H+)-ATPases — nature's most versatile proton pumpsNature Reviews Molecular Cell Biology, 2002
- Active H+ transport in the turtle urinary bladder. Coupling of transport to glucose oxidation.The Journal of general physiology, 1976