CHLORIDE-DEPENDENT NA-H EXCHANGE

The mechanism of sodium movement across apical membrane of colonic crypt cells of rat distal colon was examined in studies of both Na-22 uptake by apical membrane vesicles (AMV) and the rate of intracellular pH (pH(i)) recovery from an acid load by the addition of lumen sodium, In the presence of chloride but not in its absence, Na-22 uptake in crypt AMV was stimulated by an outward gradient of either [H+] or [Na+], Na-22 uptake stimulated by an outward [Na+] gradient was also observed in the presence of other halides in the order of chloride > bromide > fluoride > iodide, pH(i) recovery from an acid load was both lumen sodium- and chloride-dependent, and the rate of pH(i) recovery by lumen sodium in the presence of chloride was 65-fold greater than that in the absence of chloride (dpH/dt is 655.4 and 10.2 in the presence and absence of chloride, respectively), One mM amiloride inhibited both [H+] gradient-stimulated Na-22 uptake in the presence of chloride in crypt AMV (80%) and lumen sodium- and chloride-dependent pH(i) recovery in crypt cells (96%), [H+] gradient stimulation of Na-22 uptake by crypt AMV in the presence of chloride was less sensitive to amiloride than amiloride inhibition of Na-H exchange in colonic surface AMV. These studies provide compelling evidence that a chloride dependent Na-H exchange that is relatively amiloride-resistant is present in the apical membrane of colonic crypt cells, As prior studies have not identified a chloride-dependent Na-H exchange, the molecular and functional basis of this novel transport process is not known.