Amiloride sensitivity of the transepithelial electrical potential and of sodium and potassium transport in rat distal colon in vivo.

Abstract

The effect of amiloride [a pyrazine diuretic] within the gut lumen on the transepithelial electrical potential difference (p.d.) and Na and K transport by the distal colon of adrenalectomized (dexamethasone-maintained), normal, aldosterone-infused and Na-depleted groups of rats was examined. Amiloride had no effect in adrenalectomized rats; in normal rats, only the p.d. was significantly reduced. In the group given a short (2 h) aldosterone infusion, amiloride reduced the elevated p.d. and K secretion rate to normal levels. There was no change in apparent K permeability of the epithelium. In the Na-depleted group, p.d. and Na absorption were virtually abolished by amiloride, but although K secretion was reduced, it still remained much above normal levels. Adrenalectomy prevented the effects of Na depletion. P.d. change occurred rapidly when amiloride was added to the perfusate. Increasing the Na concentration in the perfusate reduced the sensitivity to amiloride. Apparent Km values estimated from p.d. changes (luminal Na, 50 mM) were similar for aldosterone-infused (7.6 .times. 10-6 M) and Na-depleted (5.4 .times. 10-6 M) rats. Aldosterone is apparently essential for the induction of amiloride-sensitive Na paths in the mucosal plasma membrane of rat colonic epithelial cells. Prolonged aldosterone stimulation, as in the Na-depleted rats, increases the amiloride-sensitive Na paths while largely suppressing the amiloride-insensitive Na paths; in addition, the K/Na clearance rate ratio of the epithelium is increased. Amiloride interacts only with 1 set of Na paths and does not interact directly with K paths.