CHLORIDE-DEPENDENT NA-H EXCHANGE

The mechanism of sodium movement across apical membrane of colonic cry pt cells of rat distal colon was examined in studies of both Na-22 upt ake by apical membrane vesicles (AMV) and the rate of intracellular pH (pH(i)) recovery from an acid load by the addition of lumen sodium, I n the presence of chloride but not in its absence, Na-22 uptake in cry pt 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 so dium- 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 th e absence of chloride (dpH/dt is 655.4 and 10.2 in the presence and ab sence 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 a miloride inhibition of Na-H exchange in colonic surface AMV. These stu dies provide compelling evidence that a chloride dependent Na-H exchan ge that is relatively amiloride-resistant is present in the apical mem brane of colonic crypt cells, As prior studies have not identified a c hloride-dependent Na-H exchange, the molecular and functional basis of this novel transport process is not known.