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 (Isc), 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 (DFCl), and luminal ATP induced a change in Isc opposite in polarity to Cl- secretion. Intracellular microelectrode measurements indicated that the "reversed" Isc was associated with activation of a hyperpolarizing (K+) conductance in the apical membrane. Radioisotope studies of HAE pretreated with amiloride to induce a favorable DFCl 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 (approximately 10(-6) M). We conclude that luminal ATP activates an apical membrane K+ conductance and transepithelial K+ secretion across HAE.
Clarke
L L
LL
Dalton Cardiovascular Research Center, University of Missouri-Columbia 65211, USA.
Chinet
T
T
Boucher
R C
RC
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*
D018118:Chloride Channels; D002712:Chlorides; D000584:Amiloride; D000255:Adenosine Triphosphate; D011188:Potassium