1. The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation.
- Author
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Joskova M, Sutovska M, Durdik P, Koniar D, Hargas L, Banovcin P, Hrianka M, Khazaei V, Pappova L, and Franova S
- Subjects
- Animals, Asthma chemically induced, Asthma drug therapy, Asthma metabolism, Calcium Channel Blockers pharmacology, Cilia drug effects, Disease Models, Animal, Guinea Pigs, Hypersensitivity drug therapy, Hypersensitivity etiology, Hypersensitivity metabolism, Hypersensitivity pathology, Inflammation chemically induced, Inflammation drug therapy, Inflammation metabolism, Ion Channels metabolism, Male, Ovalbumin toxicity, Respiratory Mucosa drug effects, Trachea drug effects, Asthma pathology, Cilia physiology, Inflammation pathology, Ion Channels antagonists & inhibitors, Respiratory Mucosa physiology, Trachea physiology
- 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.
- Published
- 2016
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