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 Ca(2+) homeostasis in Paramecium, cardiomyocytes and neurons. Since ciliary beat frequency (CBF) in the trachea is known to be increased by cytoplasmic Ca(2+) 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 microM, while it did not do so at 30 microM. At 100 microM, it increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in mouse tracheal ciliary cells. In Ca(2+)-free solution, PFOS at 100 microM failed to increase CBF (0.96-fold of vehicle control). The addition of Gd(3+) (1 microM), a store-operated Ca(2+) 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 [Ca(2+)](i), increased CBF by 20% (P<0.05). This observation indicates involvement of voltage-dependent Ca(2+) channels (VDCCs) in stimulation of CBF. Nifedipine (30 microM), 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 alpha (PPARalpha)-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 PPARalpha. These findings collectively suggest that PFOS stimulates CBF by increasing cytoplasmic Ca(2+) through VDCC.