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.