Abstract

The human respiratory tract is constantly exposed to polycyclic aromatic hydrocarbons (PAHs) through inhalation of atmospheric pollutants. We examined the effects of three PAHs (benzo[a]pyrene, anthracene, and fluoranthene) on the airway ion transport, which is essential for lung defense and normal airway function, using human airway epithelia (Calu-3). These three PAHs had no significant effect on the basal short-circuit current (I_sc). However, fluoranthene (1–100 μM) applied in the apical compartment potentiated I_sc in response to cAMP-related agents (isoproterenol, forskolin, and 8-bromo-cAMP). The effects of fluoranthene were unaffected by ellipticine, a PAH receptor antagonist. Estimation of the anionic composition of I_sc revealed that isoproterenol increased both and Cl^– transport in the control, whereas it potentiated only Cl^– transport in the presence of fluoranthene. The fluoranthene-induced modulations of these anion transporters were counteracted by charybdotoxin (ChTx, a hIK-1 channel blocker). Fluoranthene gradually augmented the ChTx-sensitive K⁺ current (I_K) across the basolateral membrane, accompanied by a sustained increase in the cytosolic Ca²⁺ concentration ([Ca²⁺]_i). In the presence of fluoranthene, however, a much larger hIK-1-dependent I_K was identified by the application of 8-bromo-cAMP without concomitant elevation of [Ca²⁺]_i. These results suggest that fluoranthene switches from cAMP-dependent secretion to Cl^– secretion through the hIK-1 channel, whose sensitivity to protein kinase A may be up-regulated by the sustained [Ca²⁺]_i elevation produced by this chemical.