Skip to main content
SpringerLink
Log in

Kv7 (KCNQ) Potassium Channels and L-type Calcium Channels in the Regulation of Airway Diameter

  • Chapter
  • First Online:
Calcium Signaling In Airway Smooth Muscle Cells

Abstract

Potassium channels in airway smooth muscle cells (ASMCs) help to maintain negative membrane voltages and thereby oppose the opening of voltage-sensitive calcium channels (VSCCs). There is considerable evidence that an influx of calcium ions (Ca2+) through L-type VSCCs contributes to induce contraction of ASMCs and bronchoconstriction of small airways, both physiologically and in diseases such as asthma in which exaggerated bronchoconstrictor responses are evident. Suppression of potassium channel activity is one mechanism to promote Ca2+ influx via VSCCs, though little is known regarding the involvement of potassium channels in bronchoconstrictor signal transduction. Pharmacological enhancement of potassium channel activity is expected to reduce Ca2+ influx via VSCCs and relax airways, though no K+ channel activators have yet been successfully developed as therapies for asthma. This chapter summarizes recent evidence that Kv7 (KCNQ family) voltage-activated K+ channels are expressed in ASMCs and that they serve as signal transduction intermediates in the actions of bronchoconstrictor agonists. The extent to which these channels contribute to regulation of airway diameter, the contributions of L-type VSCCs, and the potential to develop novel bronchodilator therapies based on these biochemical pathways are also discussed.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

References

  1. Hirota, S. et al. (2007) Ionic mechanisms and Ca2+ handling in airway smooth muscle, Eur Respir J 30 (1), 114–133.

    Article  PubMed  CAS  Google Scholar 

  2. Abdullah, N.A. et al. (1994) Contraction and depolarization induced by fetal bovine serum in airway smooth muscle, Am J Physiol Lung Cell Mol Physiol 266 (5), L528–L535.

    CAS  Google Scholar 

  3. Xiao, J.-H. et al. (2010) Functional Role of Canonical Transient Receptor Potential 1 and Canonical Transient Receptor Potential 3 in Normal and Asthmatic Airway Smooth Muscle Cells, Am. J. Respir. Cell Mol. Biol. 43 (1), 17–25.

    Article  PubMed  CAS  Google Scholar 

  4. Lee, H.K. et al. (1989) Electromechanical effects of leukotriene D4 on ferret tracheal muscle and its muscarinic responsiveness, Lung 167 (3), 173–185.

    Article  PubMed  CAS  Google Scholar 

  5. Bourreau, J.P. et al. (1991) Acetylcholine Ca2+ stores refilling directly involves a dihydropyridine-sensitive channel in dog trachea, Am J Physiol Cell Physiol 261 (3), C497–C505.

    CAS  Google Scholar 

  6. Farley, J.M. et al. (1977) Role of depolarization in acetylcholine-induced contractions of dog trachealis muscle, J Pharmacol Exp Ther 201 (1), 199–205.

    PubMed  CAS  Google Scholar 

  7. Janssen, L.J. (2002) Ionic mechanisms and Ca2+ regulation in airway smooth muscle contraction: do the data contradict dogma?, Am J Physiol Lung Cell Mol Physiol 282 (6), L1161–L1178.

    PubMed  CAS  Google Scholar 

  8. An, S.S. et al. (2007) Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma, Eur Respir J 29 (5), 834–860.

    Article  PubMed  CAS  Google Scholar 

  9. Hirota, J.A. et al. (2009) Airway smooth muscle in asthma: Phenotype plasticity and function, Pulm Pharmacol Ther. 22 (5), 370–378.

    Article  PubMed  CAS  Google Scholar 

  10. Meurs, H. et al. (2008) Airway hyperresponsiveness in asthma: lessons from in vitro model systems and animal models, Eur Respir J 32 (2), 487–502.

    Article  PubMed  CAS  Google Scholar 

  11. Liu, X.S. et al. (2005) Potassium channels in airway smooth muscle and airway hyperreactivity in asthma, Chin Med J (Engl) 118 (7), 574–580.

    CAS  Google Scholar 

  12. Malerba, M. et al. (2010) The potential therapeutic role of potassium channel modulators in asthma and chronic obstructive pulmonary disease, Journal of Biological Regulators & Homeostatic Agents 24 (2), 123–130.

    CAS  Google Scholar 

  13. Brueggemann, L.I. et al. (2012) Kv7 potassium channels in airway smooth muscle cells: signal transduction intermediates and pharmacological targets for bronchodilator therapy, Am J Physiol Lung Cell Mol Physiol 302 (1), L120–L132.

    Article  PubMed  CAS  Google Scholar 

  14. Kotlikoff, M.I. (1988) Calcium currents in isolated canine airway smooth muscle cells, Am J Physiol Cell Physiol 254 (6), C793–C801.

    CAS  Google Scholar 

  15. Worley, J.F. et al. (1990) Dihydropyridine-sensitive single calcium channels in airway smooth muscle cells, Am J Physiol Lung Cell Mol Physiol 259 (6), L468–L480.

    CAS  Google Scholar 

  16. Du, W. et al. (2006) Excitation-Contraction Coupling in Airway Smooth Muscle, J Biol Chem 281 (40), 30143–30151.

    Article  PubMed  CAS  Google Scholar 

  17. Janssen, L.J. (1997) T-type and L-type Ca2+ currents in canine bronchial smooth muscle: characterization and physiological roles, Am J Physiol Cell Physiol 272 (6), C1757–C1765.

    CAS  Google Scholar 

  18. Wang, Y.X. et al. (1997) Modulation of maxi-K+ channels by voltage-dependent Ca2+ channels and methacholine in single airway myocytes, Am J Physiol Cell Physiol 272 (4), C1151–C1159.

    CAS  Google Scholar 

  19. Liu, X. et al. (1996) Acetylcholine-induced chloride current oscillations in swine tracheal smooth muscle cells, J Pharmacol Exp Ther 276 (1), 178–186.

    PubMed  CAS  Google Scholar 

  20. Kumasaka, D. et al. (1996) MgSO4 relaxes porcine airway smooth muscle by reducing Ca2+ entry, Am J Physiol Lung Cell Mol Physiol 270 (3), L469–L474.

    CAS  Google Scholar 

  21. Ressmeyer, A.-R. et al. (2010) Human Airway Contraction and Formoterol-Induced Relaxation Is Determined by Ca2+ Oscillations and Ca2+ Sensitivity, Am. J. Respir. Cell Mol. Biol. 43 (2), 179–191.

    Article  PubMed  CAS  Google Scholar 

  22. Hay, D.W. et al. (1999) Endothelin receptors and calcium translocation pathways in human airways, Naunyn Schmiedebergs Arch Pharmacol. 359 (5), 404–410.

    Article  PubMed  CAS  Google Scholar 

  23. Kohrogi, H. et al. (1985) Nifedipine inhibits human bronchial smooth muscle contractions induced by leukotrienes C4 and D4, prostaglandin F2 alpha, and potassium, Am Rev Respir Dis 132 (2), 299–304.

    PubMed  CAS  Google Scholar 

  24. Solway, J. et al. (1985) Differential inhibition of bronchoconstriction by the calcium channel blockers, verapamil and nifedipine, Am Rev Respir Dis. 132 (3), 666–670.

    PubMed  CAS  Google Scholar 

  25. Fish, J.E. (1984) Calcium channel antagonists in the treatment of asthma, J Asthma 21 (6), 407–418.

    Article  PubMed  CAS  Google Scholar 

  26. Lei, Y. et al. (2011) Enhanced airway smooth muscle cell thromboxane receptor signaling via activation of JNK MAPK and extracellular calcium influx, Eur J Pharmacol. 650 (2–3), 629–638.

    Article  PubMed  CAS  Google Scholar 

  27. Dai, J.M. et al. (2007) Acetylcholine-induced asynchronous calcium waves in intact human bronchial muscle bundle, Am J Respir Cell Mol Biol. 36 (5), 600–608.

    Article  PubMed  CAS  Google Scholar 

  28. Moura, C.T. et al. (2005) Increased responsiveness to 5-hydroxytryptamine after antigenic challenge is inhibited by nifedipine and niflumic acid in rat trachea in vitro, Clin Exp Pharmacol Physiol. 32 (12), 1119–1123.

    Article  PubMed  CAS  Google Scholar 

  29. Hirota, K. et al. (2003) Effects of three different L-type Ca2+ entry blockers on airway constriction induced by muscarinic receptor stimulation, Br J Anaesth. 90 (5), 671–675.

    Article  PubMed  CAS  Google Scholar 

  30. Matsuda, F. et al. (2000) Comparative effect of amrinone, aminophylline and diltiazem on rat airway smooth muscle, Acta Anaesthesiol Scand. 44 (6), 763–766.

    Article  PubMed  CAS  Google Scholar 

  31. Thirstrup, S. et al. (1997) In vitro studies on the interactions of beta2-adrenoceptor agonists, methylxanthines, Ca2+-channel blockers, K+-channel openers and other airway smooth muscle relaxants in isolated guinea-pig trachea, Eur J Pharmacol. 326 (2–3), 191–200.

    Article  PubMed  CAS  Google Scholar 

  32. Ahmed, T. et al. (1992) Modification of histamine- and methacholine-induced bronchoconstriction by calcium antagonist gallopamil in asthmatics, Respiration 59 (6), 332–338.

    Article  PubMed  CAS  Google Scholar 

  33. Vannier, C. et al. (1995) Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle, Am J Physiol Lung Cell Mol Physiol 268 (2), L201–L206.

    CAS  Google Scholar 

  34. Fanta, C.H. (1985) Calcium-channel blockers in prophylaxis and treatment of asthma, Am J Cardiol 55 (3), 202B–209B.

    Article  PubMed  CAS  Google Scholar 

  35. Perez-Zoghbi, J.F. et al. (2009) Ion channel regulation of intracellular calcium and airway smooth muscle function, Pulm Pharmacol Ther. 22 (5), 388–397.

    Article  PubMed  CAS  Google Scholar 

  36. Janssen, L.J. (2009) Asthma therapy: how far have we come, why did we fail and where should we go next?, Eur Respir J 33 (1), 11–20.

    Article  PubMed  CAS  Google Scholar 

  37. Li, Q.J. et al. (2002) Membrane currents in canine bronchial artery and their regulation by excitatory agonists, Am J Physiol Lung Cell Mol Physiol 282 (6), L1358-L1365.

    PubMed  CAS  Google Scholar 

  38. Yamakage, M. et al. (1995) Cholinergic regulation of voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells, Am J Physiol Lung Cell Mol Physiol 269 (6), L776–L782.

    CAS  Google Scholar 

  39. Farley, J.M. et al. (1978) The sources of calcium for acetylcholine-induced contractions of dog tracheal smooth muscle, J Pharmacol Exp Ther 207 (2), 340–346.

    PubMed  CAS  Google Scholar 

  40. Barnes, P.J. (1985) Clinical studies with calcium antagonists in asthma, Br. J. Clin. Pharmacol. 20 (Suppl 2), 289S–298S.

    Google Scholar 

  41. Henderson, K.K. et al. (2007) Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways, J Appl Physiol. 102 (4), 1402–1409.

    Article  PubMed  CAS  Google Scholar 

  42. Byron, K.L. (1996) Vasopressin stimulates Ca2+ spiking activity in A7r5 vascular smooth muscle cells via activation of phospholipase A2, Circ Res 78 (5), 813–820.

    Article  PubMed  CAS  Google Scholar 

  43. Mackie, A.R. et al. (2008) Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction by vasopressin, based on studies in single cells, pressurized arteries, and in vivo measurements of mesenteric vascular resistance, J Pharmacol Exp Ther 325 (2), 475–483.

    Article  PubMed  CAS  Google Scholar 

  44. Mani, B.K. et al. (in press) Vascular KCNQ (Kv7) potassium channels as common signaling intermediates and therapeutic targets in cerebral vasospasm., J. Cardiovasc. Pharmacol.

    Google Scholar 

  45. Liu, C. et al. (2005) Regulation of Rho/ROCK signaling in airway smooth muscle by membrane potential and [Ca2+]i, Am J Physiol Lung Cell Mol Physiol 289 (4), L574–L582.

    Article  PubMed  CAS  Google Scholar 

  46. Parekh, A.B.. (2008) Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function, The Journal of Physiology 586 (13), 3043–3054.

    Article  PubMed  CAS  Google Scholar 

  47. Patakas, D. et al. (1983) Nifedipine in bronchial asthma, J Allergy Clin Immunol. 72 (3), 269–273.

    Article  PubMed  CAS  Google Scholar 

  48. Schwartzstein, R.S. et al. (1986) Orally administered nifedipine in chronic stable asthma. Comparison with an orally administered sympathomimetic, Am Rev Respir Dis. 134 (2), 262–265.

    PubMed  CAS  Google Scholar 

  49. Hall, I.P. (2000) Second messengers, ion channels and pharmacology of airway smooth muscle, Eur Respir J 15 (6), 1120–1127.

    Article  PubMed  CAS  Google Scholar 

  50. Maljevic, S. et al. (2008) Nervous system Kv7 disorders: breakdown of a subthreshold brake, J Physiol 586 (7), 1791–1801.

    Article  PubMed  CAS  Google Scholar 

  51. Peroz, D. et al. (2008) Kv7.1 (KCNQ1) properties and channelopathies, J Physiol 586 (7), 1785–1789.

    Article  PubMed  CAS  Google Scholar 

  52. Henderson, K.K. et al. (2007) Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways, J Appl Physiol 102 (4), 1402–1409.

    Article  PubMed  CAS  Google Scholar 

  53. Brueggemann, L.I. et al. (2007) Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells, Am J Physiol Heart Circ Physiol 292 (3), H1352–H1363.

    Article  PubMed  CAS  Google Scholar 

  54. Yeung, S.Y. et al. (2007) Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity, Br. J. Pharmacol. 151 (6), 758–770.

    Article  PubMed  CAS  Google Scholar 

  55. Joshi, S. et al. (2006) Pulmonary vasoconstrictor action of KCNQ potassium channel blockers, Respir Res 7, 31.

    Article  PubMed  Google Scholar 

  56. Joshi, S. et al. (2009) KCNQ Modulators Reveal a Key Role for KCNQ Potassium Channels in Regulating the Tone of Rat Pulmonary Artery Smooth Muscle, J Pharmacol Exp Ther 329 (1), 368–376.

    Article  PubMed  CAS  Google Scholar 

  57. Devulder, J. (2010) Flupirtine in pain management: pharmacological properties and clinical use, CNS Drugs 24 (10), 867–881.

    Article  PubMed  CAS  Google Scholar 

  58. Brueggemann, L.I. et al. (2010) Novel Actions of Nonsteroidal Anti-Inflammatory Drugs on Vascular Ion Channels: Accounting for Cardiovascular Side Effects and Identifying New Therapeutic Applications, Molecular and Cellular Pharmacology 2 (1), 15–19.

    PubMed  CAS  Google Scholar 

  59. Brueggemann, L.I. et al. (2009) Differential effects of selective cyclooxygenase-2 inhibitors on vascular smooth muscle ion channels may account for differences in cardiovascular risk profiles, Mol Pharmacol 76 (5), 1053–1061.

    Article  PubMed  CAS  Google Scholar 

  60. Mani, B.K. et al. (2011) Activation of vascular KCNQ (Kv7) potassium channels reverses spasmogen-induced constrictor responses in rat basilar artery, British Journal of Pharmacology 164, 237–249.

    Article  PubMed  CAS  Google Scholar 

  61. Wang, Y.X. et al. (2011) Molecular expression and functional role of canonical transient receptor potential channels in airway smooth muscle cells, Adv Exp Med Biol 704, 731–747.

    Article  PubMed  CAS  Google Scholar 

  62. Daniel, E.E. et al. (1993) Chloride and depolarization by acetylcholine in canine airway smooth muscle, Can J Physiol Pharmacol 71 (3–4), 284–292.

    Article  PubMed  CAS  Google Scholar 

  63. Bal, M. et al. (2008) Homomeric and Heteromeric Assembly of KCNQ (Kv7) K+ Channels Assayed by Total Internal Reflection Fluorescence/Fluorescence Resonance Energy Transfer and Patch Clamp Analysis, J Biol Chem 283 (45), 30668–30676.

    Article  PubMed  CAS  Google Scholar 

  64. Schwake, M. et al. (2003) A carboxy-terminal domain determines the subunit specificity of KCNQ K+ channel assembly, EMBO Rep. 4 (1), 76–81.

    Article  PubMed  CAS  Google Scholar 

  65. Brueggemann, L.I. et al. (2011) Diclofenac distinguishes among homomeric and heteromeric potassium channels composed of KCNQ4 and KCNQ5 subunits, Mol Pharmacol 79 (1), 10–23.

    Article  PubMed  CAS  Google Scholar 

  66. Delmas, P. et al. (2005) Pathways modulating neural KCNQ/M (Kv7) potassium channels, Nat Rev Neurosci 6 (11), 850–862.

    Article  PubMed  CAS  Google Scholar 

  67. Fan, J. et al. (2000) Ca2+ signalling in rat vascular smooth muscle cells: a role for protein kinase C at physiological vasoconstrictor concentrations of vasopressin, J Physiol 524 Pt 3, 821–831.

    Article  PubMed  CAS  Google Scholar 

  68. Hernandez, C.C. et al. (2008) Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications, J Physiol 586 (7), 1811–1821.

    Article  PubMed  CAS  Google Scholar 

  69. Schroeder, B.C. et al. (1998) Moderate loss of function of cyclic-AMP-modulated KCNQ2/KCNQ3 K+ channels causes epilepsy, Nature 396 (6712), 687–690.

    Article  PubMed  CAS  Google Scholar 

  70. Chambard, J.M. et al. (2005) Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway, Pflugers Arch 450 (1), 34–44.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology & Therapeutics, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL, 60153, USA

    Kenneth L. Byron, Lioubov I. Brueggemann, Priyanka P. Kakad & Jennifer M. Haick

Authors
  1. Kenneth L. Byron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lioubov I. Brueggemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Priyanka P. Kakad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jennifer M. Haick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth L. Byron .

Editor information

Editors and Affiliations

  1. Albany Medical College Center for Cardiovascular Sciences, Albany, New York, USA

    Yong-Xiao Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Byron, K.L., Brueggemann, L.I., Kakad, P.P., Haick, J.M. (2014). Kv7 (KCNQ) Potassium Channels and L-type Calcium Channels in the Regulation of Airway Diameter. In: Wang, YX. (eds) Calcium Signaling In Airway Smooth Muscle Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-01312-1_2

Download citation

Publish with us

Policies and ethics

Search

Navigation