Potassium Ion Channels and Allergic Asthma
- 15 October 2014
- book chapter
- Published by Springer Nature
- Vol. 838, 35-45
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.Keywords
This publication has 20 references indexed in Scilit:
- CRAC Ion Channels and Airway Defense Reflexes in Experimental Allergic Inflammation2012
- Relationship Between Potassium Ion Channels and Airways Defence Reflexes Influenced by Experimentally Induced Allergic Inflammation in Guinea PigsActa Medica Martiniana, 2012
- Ion Channels in AsthmaJournal of Biological Chemistry, 2011
- Ion channel regulation of intracellular calcium and airway smooth muscle functionPulmonary Pharmacology & Therapeutics, 2009
- Interleukin-4 activates large-conductance, calcium-activated potassium (BKCa) channels in human airway smooth muscle cellsExperimental Physiology, 2008
- Regulation of Mammalian Ciliary BeatingAnnual Review of Physiology, 2007
- K channel therapeutics at the bedsideJournal of Molecular and Cellular Cardiology, 2005
- Ions and blockers in potassium channels: insights from free energy simulationsBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2005
- Potential role of potassium channel openers in the treatment of asthma and chronic obstructive pulmonary diseaseLife Sciences, 2002
- Calcium sensors as new therapeutic targets for airway hyperresponsiveness and asthmaThe FASEB Journal, 2001