ATP-activated basolateral Na+/H+ exchange in human normal and cystic fibrosis airway epithelium

This study investigated the distribution (apical/basolateral membrane) of Na+/H+ exchange in human nasal epithelial cell monolayers from cystic fibrosis (CF) and non-CF individuals. Monolayers of non-CF and CF preparations were loaded with the pH probe 2',7' -bis(carboxyethyl)-5(6)-carboxyfluorescein, and intracellular pH (pi-Ii) was measured with a microfluorimeter. In nominally HCO3-free NaCl Ringer solution, basal pH(i) values in non-CF and CF monolayers were essentially identical(similar to 7.1). When cells were acid loaded (NH4+ prepulse), subsequent alkalinization of non-CF and CF cell monolayers required serosal Na+ and was blocked by serosal, but not mucosal, amiloride (500 mu M). In the presence of extracellular Na+, initial rates (Delta pH(i)/min) of recovery from an acid load in non-CF and CF preparations were statistically identical (similar to 0.08). Pretreatment of monolayers with ATP (100 mu M) or phorbol 12-myristate 13-acetate (PMA; 100 nM) caused initial rates of recovery to increase by twofold over control values in both preparations. These data provide evidence in support for an ATP- and PMA-activated Na+/H+ exchanger located at the basolateral surface of airway epithelia.