The Changes in Expression of NaV1.7 and NaV1.8 and the Effects of the Inhalation of Their Blockers in Healthy and Ovalbumin-Sensitized Guinea Pig Airways.

Michaela Kocmalova,Martina Sutovska,Sona Franova,Jana Barborikova,Ivana Kazimierova,Marta Joskova

doi:10.3390/membranes11070511

Michaela Kocmalova, Martina Sutovska + Show 4 more

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https://doi.org/10.3390/membranes11070511

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Journal: Membranes	Publication Date: Jul 7, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Comenius University Bratislava

Abstract

Background: The presented study evaluated the suppositional changes in the airway expression of Nav1.8 and Nav1.7 and their role in the airway defense mechanisms in healthy animals and in an experimental asthma model. Methods: The effects of the blockers inhalation on the reactivity of guinea pig airways, number of citric-acid-induced coughs and ciliary beating frequency (CBF) were tested in vivo. Chronic inflammation simulating asthma was induced by repetitive exposure to ovalbumin. The expression of Nav1.7 and Nav1.8 was examined by ELISA. Results: The Nav 1.8 blocker showed complex antitussive and bronchodilatory effects and significantly regulated the CBF in healthy and sensitized animals. The Nav1.7 blockers significantly inhibited coughing and participated in CBF control in the ovalbumin-sensitized animals. The increased expression of the respective ion channels in the sensitized animals corresponded to changes in CBF regulation. The therapeutic potency of the Nav1.8 blocker was evidenced in combinations with classic bronchodilators. Conclusion: The allergic-inflammation-upregulated expression of Nav1.7 and Nav1.8 and corresponding effects of blocker inhalation on airway defense mechanisms, along with the Nav1.8 blocker’s compatibility with classic antiasthmatic drugs, bring novel possibilities for the treatment of various respiratory diseases. However, the influence of the Nav1.8 blocker on CBF requires further investigation.

Highlights

Respiratory tract receptors and defensive reflexes, such as sneezing and coughing, have been extensively studied
Huwentoxin IV, with a preferential effect on NaV1.7, significantly reduced the number of cough efforts, especially for the middle tested concentration, at which the cough suppression lasted longer (Figure 1B), and in OVA-sensitized guinea pigs, where the suppressive effect was limited to the measurement 60 min after the drug inhalation (Figure 1E)
We proved the role of NaV1.7 and NaV1.8 in the modulation of airway defense reflexes in physiological conditions as well as during the development of allergic inflammation

Summary

Introduction

Respiratory tract receptors and defensive reflexes, such as sneezing and coughing, have been extensively studied. Studies in guinea pigs have shown that the vagal neurons innervating the respiratory tract express the NaV1.7, NaV1.8 and NaV1.9 isoforms [6,8]. The presented study evaluated the suppositional changes in the airway expression of Nav1.8 and Nav1.7 and their role in the airway defense mechanisms in healthy animals and in an experimental asthma model. Results: The Nav 1.8 blocker showed complex antitussive and bronchodilatory effects and significantly regulated the CBF in healthy and sensitized animals. The increased expression of the respective ion channels in the sensitized animals corresponded to changes in CBF regulation. Conclusion: The allergic-inflammation-upregulated expression of Nav1.7 and Nav1.8 and corresponding effects of blocker inhalation on airway defense mechanisms, along with the Nav1.8 blocker’s compatibility with classic antiasthmatic drugs, bring novel possibilities for the treatment of various respiratory diseases. The influence of the Nav1.8 blocker on CBF requires further investigation

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