Effects of perfluorooctane sulfonate on tracheal ciliary beating frequency in mice

Perfluorooctane sulfonate (PFOS) is one of the emerging persistent organic pollutants, ubiquitously found in the global environment, even in human serum. PFOS has been reported to perturb Ca2+ homeostasis in Paramecium, cardiomyocytes and neurons. Since ciliary beat frequency (CBF) in the trachea is known to be increased by cytoplasmic Ca2+ elevation, the effects of PFOS on CBF were evaluated in a slice preparation using video-enhanced contrast microscopy. PFOS increased CBF by 11% (P < 0.05) at 100 μM, while it did not do so at 30 μM. At 100 μM, it increased intracellular Ca2+ concentration ([Ca2+]i) in mouse tracheal ciliary cells. In Ca2+-free solution, PFOS at 100 μM failed to increase CBF (0.96-fold of vehicle control). The addition of Gd3+ (1 μM), a store-operated Ca2+ channel blocker, did not prevent the increase in CBF (1.09-fold (P < 0.01) of vehicle control). High extracellular K+ concentration (50 mM), which causes depolarization of the plasma membrane potential and a transient increase in [Ca2+]i, increased CBF by 20% (P < 0.05). This observation indicates involvement of voltage-dependent Ca2+ channels (VDCCs) in stimulation of CBF. Nifedipine (30 μM), a selective VDCC blocker, antagonized the effects of high K+ (0.92-fold of high K+ solution) and PFOS (0.96-fold of vehicle control) on CBF. In cells from peroxisome proliferator-activated receptor α (PPARα)-null mice, PFOS still increased CBF (1.12-fold (P < 0.05) of vehicle control), indicating that the actions of PFOS are not mediated via PPARα. These findings collectively suggest that PFOS stimulates CBF by increasing cytoplasmic Ca2+ through VDCC.