Abstract
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 μM, while it did not do so at 30 μM. At 100 μM, it increased intracellular Ca 2+ concentration ([Ca 2+] i) in mouse tracheal ciliary cells. In Ca 2+-free solution, PFOS at 100 μM failed to increase CBF (0.96-fold of vehicle control). The addition of Gd 3+ (1 μM), 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 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 Ca 2+ through VDCC.
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