Extracellular ATP stimulates K+ secretion across cultured human airway epithelium

Extracellular ATP applied to the luminal side of human airway epithelium (HAE) activates an apical membrane Cl- conductance and transepithelial Cl- secretion. However, in some HAE preparations, we have found that luminal ATP induces a change in short-circuit current (I(sc)), consistent with K+ secretion. Using intracellular microelectrodes and radioisotopic flux studies, we investigated whether extracellular ATP regulates transepithelial K+ secretion in primary HAE cultures. In physiological Ringer solution, HAE had a negligible electrochemical driving force for Cl- secretion (DF(a)/(Cl)), and luminal ATP induced a change in I(sc) opposite in polarity to Cl- secretion. Intracellular microelectrode measurements indicated that the 'reversed' I(sc) was associated with activation of a hyperpolarizing (K+) conductance in the apical membrane. Radioisotope studies of HAE pretreated with amiloride to induce a favorable DF(a)/(Cl) revealed that luminal ATP stimulates a small 42K secretory flux concurrently with Cl- secretion. In ion-substituted Ringer solution, luminal ATP stimulated both the outward (K+) current and the inward (Cl-) current with approximately equal potency (~10-6 M). We conclude that luminal ATP activates an apical membrane K+ conductance and transepithelial K+ secretion across HAE.