title: Airway Defense Control Mediated via Voltage-Gated Sodium Channels.
abstract: Expression of voltage-gated sodium channels (Nav) takes place in the airways and the role of Nav1.7 and Nav1.8 in the control of airway's defense reflexes has been confirmed. The activation of Nav channels is crucial for cough initiation and airway smooth muscle reactivity, but it is unknown whether these channels regulate ciliary beating. This study evaluated the involvement of Nav1.7 and Nav1.8 channels in the airway defense mechanisms using their pharmacological blockers in healthy guinea pigs and in the experimental allergic asthma model. Asthma was modeled by ovalbumin sensitization over a period of 21 days. Blockade of Nav1.7 channels significantly decreased airway smooth muscle reactivity in vivo, the number of cough efforts, and the cilia beat frequency in healthy animals. In the allergic asthma model, blockade of Nav1.8 efficiently relieved symptoms of asthma, without adversely affecting cilia beat frequency. The study demonstrates that Nav1.8 channel antagonism has a potential to alleviate cough and bronchial hyperreactivity in asthma.
authors.affiliation: Department of Pharmacology, Division of Respirology, 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: Kocmalova
authors.affiliation: Department of Pharmacology, Division of Respirology, 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, Division of Respirology, 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
authors.affiliation: Department of Children and Adolescents, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, and Martin University Hospital, Martin, Slovakia.
authors.forename: P
authors.initials: P
authors.lastname: Banovcin
authors.affiliation: Department of Pharmacology, Division of Respirology, 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
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010047:Ovalbumin / Q000633:toxicity; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000378:metabolism
chemical_list: D026941:Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels; D010047:Ovalbumin
keywords: Airways; Asthma; Bronchial hyperreactivity; Ciliary beat frequency; Cough; Voltage-gated sodium channels