Novel regulation of cell [Na(+)] in macula densa cells: apical Na(+) recycling by H-K-ATPase.
Na-K-ATPase is the nearly ubiquitous enzyme that maintains low-Na(+), high-K(+) concentrations in cells by actively extruding Na(+) in exchange for K(+). The prevailing paradigm in polarized absorbing epithelial cells, including renal nephron segments and intestine, has been that Na-K-ATPase is restricted to the basolateral membrane domain, where it plays a prominent role in Na(+) absorption. We have found, however, that macula densa (MD) cells lack functionally and immunologically detectable amounts of Na-K-ATPase protein. In fact, these cells appear to regulate their cytosolic [Na(+)] via another member of the P-type ATPase family, the colonic form of H-K-ATPase, which is located at the apical membrane in these cells. We now report that this constitutively expressed apical MD colonic H-K-ATPase can function as a Na(H)-K-ATPase and regulate cytosolic [Na(+)] in a novel manner. This apical Na(+)-recycling mechanism may be important as part of the sensor function of MD cells and represents a new paradigm in cell [Na(+)] regulation.
Peti-Peterdi
János
J
Nephrology Research and Training Center, Division of Nephrology, Department of Medicine and Physiology, and Gregory Flaming James Cystic Fibrosis Research Center, University of Alabama at Birmingham 35294, USA.
Bebok
Zsuzsa
Z
Lapointe
Jean-Yves
JY
Bell
P Darwin
PD
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D003106:Colon / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000201:enzymology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000378:metabolism
D001572:Benzofurans; D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D005456:Fluorescent Dyes; D007093:Imidazoles; C035235:Sch 28080; C061665:sodium-binding benzofuran isophthalate; D010042:Ouabain; D012964:Sodium; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase