Advertisement

Airway Defense Control Mediated via Voltage-Gated Sodium Channels

  • M. Kocmalova
  • M. JoskovaEmail author
  • S. Franova
  • P. Banovcin
  • M. Sutovska
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 921)

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.

Keywords

Airways Asthma Bronchial hyperreactivity Ciliary beat frequency Cough Voltage-gated sodium channels 

Notes

Acknowledgments

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.

References

  1. Cummins TR, Howe JR, Waxman SG (1998) Slow closed-state inactivation: a novel mechanism underlying ramp currents in cells expressing the HNE/PN1 sodium channel. J Neurosci 18:9607–9619PubMedGoogle Scholar
  2. Eljamal M, Wong LB, Yeates DB (1985) Capsaicin-activated bronchial- and alveolar-initiated pathways regulating tracheal ciliary beat frequency. J Appl Physiol 77:1239–1245Google Scholar
  3. Hargaš L, Koniar D, Štofan S (2011) Sophisticated biomedical tissue measurement using image analysis and virtual instrumentation, practical applications and solutions using LabVIEW™ software, Dr. Silviu Folea (ed) ISBN: 978-953-307-650-8, InTech, Available from: http://www.intechopen.com/books/practical-applications-and-solutions-using-labview-software/sophisticatedbiomedical-tissue-measurement-using-image-analysis-and-virtual-instrumentation
  4. Jo T, Nagata T, Iida H, Imuta H, Iwasawa K, Ma J, Hara K, Omata M, Nagai R, Takaziwa H, Nagase T, Nakajima T (2004) Voltage-gated sodium channel expressed in cultured human smooth muscle cells: involvement of SCN9A. FEBS Lett 567:339–343CrossRefPubMedGoogle Scholar
  5. Joshi SK, Honore P, Hernandez G, Schmidt R, Gomtsyan A, Scanio M, Kort M, Jarvis MF (2009) Additive antinociceptive effects of the selective Nav1.8 blocker A803467 and selective TRPV1 antagonists in rat inflammatory and neuropathic pain models. J Pain 10:306–315CrossRefPubMedGoogle Scholar
  6. Karlsson JA, Sant’Ambrogio G, Widdicombe J (1988) Afferent neural pathways in cough and reflex bronchoconstriction. J Appl Physiol 65:1007–1023PubMedGoogle Scholar
  7. Kollarik M, Dinh QT, Fischer A, Undem BJ (2003) Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibers in the mouse. J Physiol 551:869–879CrossRefPubMedPubMedCentralGoogle Scholar
  8. Kwong K, Carr MJ (2015) Voltage-gated sodium channels. Curr Opin Pharmacol 22:131–139CrossRefPubMedGoogle Scholar
  9. Kwong K, Lee LY (2005) Prostaglandin E2 potentiates a TTX resistant sodium current in rat capsaicin-sensitive vagal pulmonary sensory neurones. J Physiol 564:437–450CrossRefPubMedPubMedCentralGoogle Scholar
  10. Kwong K, Carr MJ, Cibbard A, Savage TJ, Singh K, Jing J, Meeker S, Undem BJ (2008) Voltage-gated sodium channels in nociceptive versus non-nociceptive nodose vagal sensory neurons innervating Guinea pig lungs. J Physiol 586:1321–1336CrossRefPubMedPubMedCentralGoogle Scholar
  11. Lorenzo IM, Liedtke W, Sanderson MJ, Valverde MA (2008) TRPV4 channel participates in receptor-operated calcium entry and ciliary beat frequency regulation in mouse airway epithelial cells. Proc Natl Acad Sci U S A 105:12611–12616CrossRefPubMedPubMedCentralGoogle Scholar
  12. Muroi Y, Undem BJ (2011) Targeting peripheral afferent nerve terminals for cough and dyspnoe. Curr Opin Pharmacol 11:254–264CrossRefPubMedPubMedCentralGoogle Scholar
  13. Muroi Y, Undem BJ (2014) Targeting voltage gated sodium channels NaV1.7, NaV1.8, and NaV1.9 for treatment of pathological cough. Lung 192:15–20CrossRefPubMedGoogle Scholar
  14. Muroi Y, Ru F, Kollarik M, Canning BJ, Hughes SA, Walsh S, Sigg M, Carr MJ, Undem BJ (2011) Selective silencing of NaV1.7 decreases excitability and conduction in vagal sensory neurons. J Physiol 589:5663–5676CrossRefPubMedPubMedCentralGoogle Scholar
  15. Narula M, McGovern AE, Yang SK, Farrell MJ, Mazzone SB (2014) Afferent neural pathways mediating cough in animals and humans. J Thorac Dis 6:712–719Google Scholar
  16. Pennock BE, Cox CP, Rogers RM, Cain WA, Wells JH (1979) A non-invasive technique for measurement of changes in specific airway resistance. J App Physiol 46:399–406Google Scholar
  17. Priest BT (2009) Future potential and status of selective sodium channel blockers for the treatment of pain. Curr Opin Drug Discov Devel 12:682–692PubMedGoogle Scholar
  18. Undem BJ, Carr MJ (2010) Targeting primary afferent nerves for novel antitussive therapy. Chest 137:177–184CrossRefPubMedGoogle Scholar
  19. Undem BJ, Kollarik M (2005) The role of vagal afferent nerves in chronic obstructive pulmonary disease. Proc Am Thorac Soc 2:355–360CrossRefPubMedPubMedCentralGoogle Scholar
  20. Vetter I, Mozar CA, Durek T, Wingerd JS, Alewood PF, Christie MJ, Lewis RJ (2012) Characterisation of Nav types endogenously expressed in human SH-SYSY neuroblastoma cells. Biochem Pharmacol 83:1562–1571CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • M. Kocmalova
    • 1
  • M. Joskova
    • 1
    Email author
  • S. Franova
    • 1
  • P. Banovcin
    • 2
  • M. Sutovska
    • 1
  1. 1.Department of Pharmacology, Division of Respirology, BioMed Martin, Jessenius Faculty of MedicineComenius University in BratislavaMartinSlovakia
  2. 2.Department of Children and Adolescents, Jessenius Faculty of Medicine in MartinComenius University in Bratislava, and Martin University HospitalMartinSlovakia

Personalised recommendations