title: The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation.
abstract: Overproduction of mucus is a hallmark of asthma. The aim of this study was to identify potentially effective therapies for removing excess mucus. The role of voltage-gated (Kir 6.1, KCa 1.1) and store-operated ion channels (SOC, CRAC) in respiratory cilia, relating to the tracheal ciliary beat frequency (CBF), was compared under the physiological and allergic airway conditions. Ex vivo experiments were designed to test the local effects of Kir 6.1, KCa 1.1 and CRAC ion channel modulators in a concentration-dependent manner on the CBF. Cilia, obtained with the brushing method, were monitored by a high-speed video camera and analyzed with ciliary analysis software. In natural conditions, a Kir 6.1 opener accelerated CBF, while CRAC blocker slowed it in a concentration-dependent manner. In allergic inflammation, the effect of Kir 6.1 opener was insignificant, with a tendency to decrease CBF. A cilio-inhibitory effect of a CRAC blocker, while gently reduced by allergic inflammation, remained significant. A KCa 1.1 opener turned out to significantly enhance the CBF under the allergic OVA-sensitized conditions. We conclude that optimally attuned concentration of KCa 1.1 openers or special types of bimodal SOC channel blockers, potentially given by inhalation, might benefit asthma.
authors.affiliation: Department of Pharmacology, BioMed Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 4C Mala Hora St, 036 01, Martin, Slovakia. joskova@jfmed.uniba.sk.
authors.forename: M
authors.initials: M
authors.lastname: Joskova
authors.affiliation: Department of Pharmacology, BioMed Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 4C Mala Hora St, 036 01, Martin, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Sutovska
authors.affiliation: Department of Children and Adolescents, Jessenius Faculty of Medicine, Comenius University in Bratislava and Martin University Hospital, 2 Kollarova St, 036 01, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Durdik
authors.affiliation: Department of Mechatronics and Electronics, Faculty of Electrical Engineering, University of Zilina, 1 Univerzitna St, 010 26, Zilina, Slovakia.
authors.forename: D
authors.initials: D
authors.lastname: Koniar
authors.affiliation: Department of Mechatronics and Electronics, Faculty of Electrical Engineering, University of Zilina, 1 Univerzitna St, 010 26, Zilina, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Hargas
authors.affiliation: Department of Children and Adolescents, Jessenius Faculty of Medicine, Comenius University in Bratislava and Martin University Hospital, 2 Kollarova St, 036 01, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Banovcin
authors.affiliation: Department of Mechatronics and Electronics, Faculty of Electrical Engineering, University of Zilina, 1 Univerzitna St, 010 26, Zilina, Slovakia.
authors.forename: M
authors.initials: M
authors.lastname: Hrianka
authors.affiliation: Department of Pharmacology, BioMed Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 4C Mala Hora St, 036 01, Martin, Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Khazaei
authors.affiliation: Department of Pharmacology, BioMed Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 4C Mala Hora St, 036 01, Martin, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Pappova
authors.affiliation: Department of Pharmacology, BioMed Martin, Jessenius Faculty of Medicine, Comenius University in Bratislava, 4C Mala Hora St, 036 01, Martin, Slovakia.
authors.forename: S
authors.initials: S
authors.lastname: Franova
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D010047:Ovalbumin / Q000633:toxicity; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers; D007473:Ion Channels; D010047:Ovalbumin
keywords: Asthma; Ciliary beat frequency; Mucociliary transport; Store-operated ion channels; Voltage-gated ion channels