Skip to main content

Potassium Ion Channels and Allergic Asthma

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((NR,volume 838))

Abstract

High-conductive calcium-sensitive potassium channels (BK+ Ca) and ATP-sensitive potassium (K+ ATP) channels play a significant role in the airway smooth muscle cell and goblet cell function, and cytokine production. The present study evaluated the therapeutic potential of BK+ Ca and K+ ATP openers, NS 1619 and pinacidil, respectively, in an experimental model of allergic inflammation. Airway allergic inflammation was induced with ovalbumine in guinea pigs during 21 days, which was followed by a 14-day treatment with BK+ Ca and K+ ATP openers. The outcome measures were airway smooth muscle cells reactivity in vivo and in vitro, cilia beating frequency and the level of exhaled NO (ENO), and the level of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid. The openers of both channels decreased airway smooth muscle cells reactivity, cilia beating frequency, and cytokine levels in the serum. Furthermore, NS1619 reduced ENO and inflammatory cells infiltration. The findings confirmed the presence of beneficial effects of BK+ Ca and K+ ATP openers on airway defence mechanisms. Although both openers dampened pro-inflammatory cytokines and mast cells infiltration, an evident anti-inflammatory effect was provided only by NS1619. Therefore, we conclude that particularly BK+ Ca channels represent a promising new drug target in treatment of airway’s allergic inflammation.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Bali A, Gupta S, Singh N, Jaggi AS (2013) Implicating the role of plasma membrane localized calcium channels and exchangers in stress-induced deleterious effects. Eur J Pharmacol 714:229–238

    Article  CAS  PubMed  Google Scholar 

  • Bissonette JM (2002) The role of calcium-activated potassium channels in respiratory control. Respir Physiol Neurobiol 131:145–153

    Article  Google Scholar 

  • Carr MJ, Undem BJ (2001) Ion channels in airway afferent neurons. Respir Physiol 125:83–97

    Article  CAS  PubMed  Google Scholar 

  • Deckers J, Madeira FB, Hammad H (2013) Innate immune cells in asthma. Trends Immunol 34:540–547

    Article  CAS  PubMed  Google Scholar 

  • Eisenhut M, Wallace H (2011) Ion channels in inflammation. Eur J Physiol 461:401–421

    Article  CAS  Google Scholar 

  • El-Hashim AZ, Buchheit KH, Fozard J, Page C (2004) Effect of the K+ ATP channel opener, KCO912, on baseline and allergen induced airway hyperresponsiveness in allergic rabbits. Eur J Pharmacol 484:351–356

    Article  CAS  PubMed  Google Scholar 

  • Franova S, Joskova M, Sadlonova V, Pavelcikova D, Mesarosova L, Novakova E, Sutovska M (2013) Experimental model of allergic asthma. Adv Exp Med Biol 765:49–55

    Article  Google Scholar 

  • Jahangir A, Terzic A (2005) KATP channel therapeutics at the bedside. J Mol Cell Cardiol 39:99–112

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kocmalova M, Marcinek J, Kalman M, Franova S, Sutovska M (2012) Relationship between potassium ion channels and airways defence reflexes influenced by experimentally induced allergic inflammation in Guinea pigs. Acta Med Martiniana 1:6–15

    Google Scholar 

  • Luzhkov VB, Åqvist J (2005) Ions and blockers in potassium channels: insights from free energy simulations. Biochim Biphys Acta 1747:109–120

    Article  CAS  Google Scholar 

  • Martin G, O’Connell RJ, Pietrzyzowski AZ, Treistman SN, Ethier MF, Madison JM (2008) Interleukin-4 activates large-conductance, calcium-activated potassium (BKCa) channels in human airway smooth muscle cells. Exp Physiol 93:908–918

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Pelaia G, Gallelli L, Vatrella A, Grembiale RD, Maselli R, De Sarro GB, Marsico SA (2002) Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary disease. Life Sci 70:977–990

    Article  CAS  PubMed  Google Scholar 

  • Pennock BE, Cox CP, Rogers RM, Cain WA, Wells JH (1979) A noninvasive technique for measurement of changes in specific airway resistance. J Appl Physiol 46:399–406

    CAS  PubMed  Google Scholar 

  • Perez-Zoghbi JF, Karner C, Ito S, Shephard M, Alrashdan Y, Sanderson MJ (2009) Ion channel regulation of intracellular calcium and airway smooth muscle function. Pulm Pharmacol Ther 22:388–397

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Salathe M (2007) Regulation of mammalian ciliary beating. Annu Rev Physiol 69:401–422

    Article  CAS  PubMed  Google Scholar 

  • Sutovska M, Nosalova G, Franova S (2007) The role of potassium ion channels in cough and other reflexes of the airways. J Physiol Pharmacol 58:673–683

    PubMed  Google Scholar 

  • Sutovska M, Adamkov M, Kocmalova M, Mesarosova L, Oravec M, Franova S (2013) CRAC ion channels and airway defence reflexes in experimental allergic inflammation. Adv Exp Med Biol 756:39–48

    Article  CAS  PubMed  Google Scholar 

  • Ten Broeke RT, Folkerts G, Leusink-Muis T, Van Der Linde HJ, Villain M, Manion MK, De Clerk F, Blalock JE, Nijkamp FP (2001) Calcium sensors as new therapeutic targets for airway hyperresponsiveness and asthma. FASEB J 15:1831–1833

    PubMed  Google Scholar 

  • Vaali K, Li L, Paakkari I, Vappatalo H (1998) Relaxing effect of NO donors on guinea pig trachea in in vitro are mediated by calcium-sensitive potassium channels. J Pharmacol Exp Ther 286:110–114

    CAS  PubMed  Google Scholar 

  • Valverde MA, Cantero-Recasens G, Garcia-Elias A, Jung C, Carreras-Sureda A, Vicente R (2011) Ion channels in asthma. J Biol Chem 286:32877–32882

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Weiger TM, Hermann A, Levitan IB (2002) Modulation of calcium-activated potassium channels. J Comp Physiol A 188:79–87

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Ms. Katarina Jesenska for technical support. This work was supported by the project Center of Experimental and Clinical Respirology II, the grants MZ 2012/35-UKMA-12 and VEGA No 1/0020/11 and 1/0062/11, and it was co-financed from EC sources.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Kocmalova .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Kocmalova, M. et al. (2014). Potassium Ion Channels and Allergic Asthma. In: Pokorski, M. (eds) Allergens and Airway Hyperreactivity. Advances in Experimental Medicine and Biology(), vol 838. Springer, Cham. https://doi.org/10.1007/5584_2014_76

Download citation

Publish with us

Policies and ethics