Apical and Basolateral ATP-Induced Anion Secretion in Polarized Human Airway Epithelia

The present study investigated mechanisms underlying apical and basolateral P2Y₁-mediated Cl^- secretion in human airway epithelial cells. Apical and basolateral ATP induced short-circuit currents (I_sc) with different properties via P2Y₁ receptors. The former comprised an immediate rise followed by a slow attenuation, whereas the latter was a transient rise with a higher peak and shorter duration (< 2 min). The actions of ATP were simulated by those of ADP, ADPβS, and ATP-γS. Antagonists of phosphatidylinositol-phospholipase C (U73122, ET-18-OCH₃) were without any effect on the bilateral ATP-induced I_sc, which were, in contrast, attenuated by a phosphatidylcholine- phospholipase C inhibitor (D609) and an adenylate cyclase inhibitor (SQ22536). The responses to ATP from either aspect were also sensitive to an intracellular Ca²⁺ chelator, 1,2-bis (o-amino-phenoxy)-ethane-N,N,N′, N′-tetraacetic acid tetra-(acetoxymethyl)-ester, or a Ca ²⁺-activated K⁺ channel inhibitor, charybdotoxin, although differential Ca²⁺ signals were concomitant with each reaction. Nystatin permeabilization studies revealed a good correlation between the I_sc and the basolateral K⁺ current rather than the apical Cl^- current under ATP-stimulated conditions. In conclusion, apical and basolateral P2Y₁ receptors couple with both phosphatidylcholine-phospholipase C and adenylate cyclase, leading to Cl ^- secretion, whose rate is essentially regulated by the Ca ²⁺-activated K⁺ channel-mediated K⁺ conductance. This suggests the importance of this channel in airway mucociliary clearance.