Airway Defense Control Mediated via Voltage-Gated Sodium Channels
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.
KeywordsAirways Asthma Bronchial hyperreactivity Ciliary beat frequency Cough Voltage-gated sodium 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.
Conflicts of Interest
The authors declare no conflict of interest in relation to this article.
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