The Role of Ion Channels to Regulate Airway Ciliary Beat Frequency During Allergic Inflammation
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.
KeywordsAsthma Ciliary beat frequency Mucociliary transport Store-operated ion channels Voltage-gated ion channels
This research was conducted within the project ‘Measurement of Respiratory Epithelium Cilium Kinematics’ and was supported by the grants VEGA 1/0165/14; MZ 2012/35-UK MA-12; APVV-0305-12; BioMed Martin (ITMS 26220220187); Center of Experimental and Clinical Respirology II, and ‘The increasing of opportunities for career growth in research and development in the medical sciences’, co-financed from EU sources. The authors would like to thank Katarina Jesenska for technical help during the experiments.
Conflict of Interests
All authors declared no conflicts of interest in relation to this article.
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