title: Effects of perfluorooctane sulfonate on tracheal ciliary beating frequency in mice.
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 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.
authors.affiliation: Department of Health and Environmental Sciences, Kyoto University, Graduate School of Medicine, Yoshida Konoe, Sakyo, Kyoto 6068501, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Matsubara
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahari
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kuroiwa
authors.forename: Kouji H
authors.initials: KH
authors.lastname: Harada
authors.forename: Kayoko
authors.initials: K
authors.lastname: Inoue
authors.forename: Akio
authors.initials: A
authors.lastname: Koizumi
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002923:Cilia / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D005682:Gadolinium / Q000494:pharmacology; D020868:Gene Silencing; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D018715:Microscopy, Video / Q000379:methods*; D009543:Nifedipine / Q000494:pharmacology; D009924:Organ Culture Techniques; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics; D011188:Potassium / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
chemical_list: D017738:Alkanesulfonic Acids; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004785:Environmental Pollutants; D005466:Fluorocarbons; D047493:PPAR alpha; C076994:perfluorooctane sulfonic acid; D005682:Gadolinium; D009543:Nifedipine; C038958:gadolinium chloride; D011188:Potassium; D002118:Calcium