Skip to main content
SpringerLink
Log in
Book cover

Membrane Receptors, Channels and Transporters in Pulmonary Circulation pp 3–14Cite as

The Role of Ion Channels in Hypoxic Pulmonary Vasoconstriction

  • Conference paper
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((volume 661))

Abstract

Hypoxic pulmonary vasoconstriction (HPV) is an important mechanism by which localized flow of blood in small resistance pulmonary arteries is matched to alveolar ventilation. This chapter discusses the role of several potassium and calcium channels in HPV, both in enhancing calcium influx into smooth muscle cells (SMCs) and in stimulating the release of calcium from the sarcoplasmic reticulum, thus increasing cytosolic calcium. The increase in calcium sensitivity caused by hypoxia is reviewed in Chapter 19. Particular attention is paid to the activity of the L-type calcium channels which increase calcium influx as a result of membrane depolarization and also increase calcium influx at any given membrane potential in response to hypoxia. In addition, activation of the L-type calcium channel may, in the absence of any calcium influx, cause calcium release from the sarcoplasmic reticulum. Many of these mechanisms have been reported to be involved in both HPV and in normoxic contraction of the ductus arteriosus.

This is a preview of subscription content, 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   189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
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

  1. López-Barneo J, López-López J, Ureña J, González C (1988) Chemotransduction in the carotid body: K+ current modulated by PO2 in type I chemoreceptor cells. Science 242:580-582

    Article  Google Scholar 

  2. Wyatt CN, Wright C, Bee D, Peers C (1995) O2-sensitive K+ currents in carotid body chemoreceptor cells from normoxic and chronically hypoxic rats and their role in hypoxic chemotransduction. Proc Natl Acad Sci U S A 92:295-299

    Article  PubMed  CAS  Google Scholar 

  3. Buckler KJ (1997) A novel oxygen-sensitive potassium current in rat carotid body type I cells. J Physiol 498:649-662

    PubMed  CAS  Google Scholar 

  4. Buckler KJ, Vaughan-Jones RD (1994) Effects of hypoxia on membrane potential and intracellular calcium in rat neonatal carotid body type I cells. J Physiol 476:423-428

    PubMed  CAS  Google Scholar 

  5. Ureña J, Fernández-Chacón R, Benot A, Alvarez de Toledo G, López-Barneo J (1994) Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells. Proc Natl Acad Sci U S A 91:10208-10211

    Article  PubMed  Google Scholar 

  6. Hales CA, Westphal D (1978) Hypoxemia following the administration of sublingual nitroglycerin. Am J Med 65:911-918

    Article  PubMed  CAS  Google Scholar 

  7. McMurtry I, Davidson AB, Reeves JT, Grover RF (1976) Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res 38:99-104

    Article  PubMed  CAS  Google Scholar 

  8. Harder DR, Madden JA, Dawson C (1985) A membrane electrical mechanism for hypoxic vasoconstriction of small pulmonary arteries from cat. Chest 88:233S-245S

    PubMed  CAS  Google Scholar 

  9. Ashcroft FM, Harrison DE, Ashcroft SJ (1984) Glucose induces closure of single potassium channels in isolated rat pancreatic β-cells. Nature 312:446-448

    Article  PubMed  CAS  Google Scholar 

  10. Ammon HP, Hägele R, Youssif N, Eugen R, El-Amri N (1983) A possible role of intracellular and membrane thiols of rat pancreatic islets in calcium uptake and insulin release. Endocrinology 112:720-726

    Article  PubMed  CAS  Google Scholar 

  11. Archer SL, Will JA, Weir EK (1986) Redox status in the control of pulmonary vascular tone. Hertz 11:127-141

    CAS  Google Scholar 

  12. Post JM, Hume JR, Archer SL, Weir EK (1992) Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am J Physiol 262:C882-C890

    PubMed  CAS  Google Scholar 

  13. Yuan X-J, Goldman WF, Tod ML, Rubin LJ, Blaustein MP (1993) Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes. Am J Physiol 264:L116-L123

    PubMed  CAS  Google Scholar 

  14. Coppock EA, Tamkun MM (2001) Differential expression of Kv channel α-and β-subunits in the bovine pulmonary arterial circulation. Am J Physiol Lung Cell Mol Physiol 281:L1350-L1360

    PubMed  CAS  Google Scholar 

  15. Moudgil R, Michelakis ED, Archer SL (2005) Hypoxic pulmonary vasoconstriction. J Appl Physiol 98:390-403

    Article  PubMed  CAS  Google Scholar 

  16. Archer SL, Wu XC, Thébaud B et al (2004) Preferential expression and function of voltage-gated, O2-sensitive channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells. Circ Res 95:308-318

    Article  PubMed  CAS  Google Scholar 

  17. Archer SL, London B, Hampl V et al (2001) Impairment of hypoxic pulmonary vasoconstriction in mice lacking the voltage-gated potassium channel Kv1.5. FASEB J 15:1801-1803

    PubMed  CAS  Google Scholar 

  18. Platoshyn O, Brevnova EE, Burg ED, Yu Y, Remillard CV, Yuan JX-J (2006) Acute hypoxia selectively inhibits KCNA5 channels in pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol 290:C907-C916

    Article  PubMed  CAS  Google Scholar 

  19. Platoshyn O, Yu Y, Ko EA, Remillard CV, Yuan JX-J (2007) Heterogeneity of hypoxia-mediated decrease in I K(V) and increase in [Ca2+]cyt in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 293:L402-L416

    Article  PubMed  CAS  Google Scholar 

  20. Kuebler WM, Ying X, Bhattacharya J (2002) Pressure-induced endothelial Ca2+ oscillations in lung capillaries. Am J Physiol Lung Cell Mol Physiol 282:L917-L923

    PubMed  CAS  Google Scholar 

  21. Smirnov SC, Robertson TP, Ward JPT, Aaronson PI (1994) Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells. Am J Physiol 266:H365-H370

    PubMed  CAS  Google Scholar 

  22. Osipenko ON, Alexander D, Maclean MR, Gurney AM (1998) Influence of chronic hypoxia on the contributions of non-inactivating and delayed rectifier K currents to the resting potential and tone of rat pulmonary artery smooth muscle. Br J Pharmacol 124:1335-1337

    Article  PubMed  CAS  Google Scholar 

  23. Hong Z, Weir EK, Nelson DP, Olschewski A (2004) Subacute hypoxia decrease voltage-activated potassium channel expression and function in pulmonary artery myocytes. Am J Resp Cell Mol Biol 31:1-7

    Article  Google Scholar 

  24. McMurtry IF, Petrun MD, Reeves JT (1978) Lungs from chronically hypoxic rats have decreased pressor response to acute hypoxia. Am J Physiol 235:H104-H109

    PubMed  CAS  Google Scholar 

  25. Pozeg Z, ED M, McMurtry M et al (2003) In vivo gene transfer of the O2-sensitive potassium channel Kv1.5 reduces pulmonary hypertension and restores hypoxic pulmonary vasoconstriction in chronically hypoxic rats. Circulation 107:2037-2044

    Article  PubMed  CAS  Google Scholar 

  26. Joshi S, Balan P, Gurney AM (2006) Pulmonary vasoconstrictor action of KCNQ potassium channel blockers. Respir Res 7:31-41

    Article  PubMed  Google Scholar 

  27. Gurney A, Manoury B (2009) Two-pore potassium channels in the cardiovascular system. Eur Biophys J 38:305-318

    Article  PubMed  CAS  Google Scholar 

  28. Olschewski A, Li Y, Tang B et al. (2006) Impact of TASK-1 in human pulmonary artery smooth muscle cells. Circ Res 98:1072-1080

    Article  PubMed  CAS  Google Scholar 

  29. Archer SL, Huang JMC, Reeve HL, Hampl V, Tolorová S, Michelakis E, Weir EK (1996) Differential distribution of electrophysiologically distinct myocytes in conduit and resistance arteries determines their response to nitric oxide and hypoxia. Circ Res 78:431-442

    Article  PubMed  CAS  Google Scholar 

  30. Franco-Obregon A, Lopez-Barneo J (1996) Differential oxygen sensitivity of calcium channels in rabbit smooth muscle cells of conduit and resistance pulmonary arteries. J Physiol 491:511-518

    PubMed  CAS  Google Scholar 

  31. Archer SL, Yankovich RD, Chesler E, Weir EK (1985) Comparative effects of nisoldipine, nifedipine and bepridil on experimental pulmonary hypertension. J Pharmacol Exp Ther 233:12-17

    PubMed  CAS  Google Scholar 

  32. Hoshino Y, Obara H, Kusunoki M, Fujii Y, Iwai S (1988) Hypoxic contractile response in isolated human pulmonary artery role of calcium ion. J Appl Physiol 65:2468-2474

    PubMed  CAS  Google Scholar 

  33. Salvaterra CG, Goldman WF (1993) Acute hypoxia increases cytosolic calcium in cultured pulmonary arterial myocytes. Am J Physiol 264:L323-L328

    PubMed  CAS  Google Scholar 

  34. Archer SL, Hampl V, Nelson DP, Sidney E, Peterson DA, Weir EK (1995) Dithionite increases radical formation and decreases vasoconstriction in the lung. Circ Res 77:174-181

    Article  PubMed  CAS  Google Scholar 

  35. Vadula MS, Kleinman JG, Madden JA (1993) Effect of hypoxia and norepinephrine on cytoplasmic free Ca2+ in pulmonary and cerebral arterial myocytes. Am J Physiol 265:L591-L597

    PubMed  CAS  Google Scholar 

  36. Jabr RI, Toland H, Gelband CH, Wang XX, Hume JR (1997) Prominent role of intracellular Ca2+ release in hypoxic vasoconstriction of canine pulmonary artery. Br J Pharmacol 122:21-30

    Article  PubMed  CAS  Google Scholar 

  37. Robertson TP, Hague D, Aaronson PI, Ward JPT (2000) Voltage-independent calcium entry in hypoxic pulmonary vasoconstriction of intrapulmonary arteries of the rat. J Physiol 525:669-680

    Article  PubMed  CAS  Google Scholar 

  38. Weigand L, Foxson J, Wang J, Shimoda LA, Sylvester JT (2005) Inhibition of hypoxic pulmonary vasoconstriction by store-operated Ca2+ and nonselective cation channel antagonists. Am J Physiol Lung Cell Mol Physiol 289:L5-L13

    Article  PubMed  CAS  Google Scholar 

  39. Wang J, Shimoda LA, Weigand L, Wang W, Sun D, Sylvester JT (2005) Acute hypoxia increases intracellular [Ca2+] entry. Am J Physiol Lung Cell Mol Physiol 288:L1059-L1069

    Article  PubMed  CAS  Google Scholar 

  40. Ng LC, Wilson SM, Hume JR (2005) Mobilization of sarcoplasmic reticulum stores by hypoxia leads to consequent activation of capacitative Ca2+ entry in isolated canine pulmonary arterial smooth muscle cells. J Physiol 263:409-419

    Google Scholar 

  41. Li X-Q, Zheng Y-M, Rathore R, Ma J, Takeshima H, Wang Y-X (2009) Genetic evidence for functional role of ryanodine receptor 1 in pulmonary artery smooth muscle cells. Eur J Physiol 457:771-783

    Article  CAS  Google Scholar 

  42. Zheng Y-M, Wang Q-S, Rathore R et al (2005) Type-3 ryanodine receptors mediate hypoxia-, but not neurotransmitter-induced calcium release and contraction in pulmonary artery smooth muscle cells. J Gen Physiol 125:427-440

    Article  PubMed  CAS  Google Scholar 

  43. del Valle-Rodríguez A, López-Barneo J, Ureña J (2003) Ca2+ channel-sarcoplasmic reticulum coupling: a mechanism of arterial myocyte contraction without Ca2+ influx. EMBO J 22:4337-4345

    Article  PubMed  Google Scholar 

  44. del Valle-Rodríguez A, Calderón E, Ruiz M, Ordoñez A, López-Barneo J, Ureña J (2006) Metabotropic Ca2+ channel-induced Ca2+ release and ATP-dependent facilitation of arterial myocyte contraction. Proc Natl Acad Sci U S A 103:4316-4321

    Article  PubMed  Google Scholar 

  45. Calderón-Sanchez E, Fernández-Tenorio M, Ordóñez A, López-Barneo J, Ureña J (2009) Hypoxia inhibits vasoconstriction induced by metabotropic Ca2+ channel-induced Ca2+ release in mammalian coronary arteries. Cardiovasc Res 82(1):115-124

    Article  PubMed  Google Scholar 

  46. Lu W, Wang J, Shimoda LA, Sylvester JT (2008) Differences in STIM1 and TRPC expression in proximal and distal pulmonary arterial smooth muscle are associated with differences in Ca2+ responses to hypoxia. Am J Physiol Lung Cell Mol Physiol 295:L104-L113

    Article  PubMed  CAS  Google Scholar 

  47. Weissmann N, Zeller S, Schäfer R et al (2006) Impact of mitochondria and NADPH oxidases on acute and sustained hypoxic pulmonary vasoconstriction. Am J Respir Cell Mol Biol 34:505-513

    Article  PubMed  CAS  Google Scholar 

  48. Tristani-Firouzi M, Reeve HL, Tolarova S, Weir EK, Archer SL (1996) Oxygen-induced constriction of rabbit ductus arteriosus occurs via inhibition of a 4-aminopyridine-, voltage-sensitive potassium channel. J Clin Invest 98:1959-1965

    Article  PubMed  CAS  Google Scholar 

  49. Thébaud B, Wu X-C, Kajimoto H et al (2008) Development absence of the O2 sensitivity of L-type calcium channels in preterm ductus arteriosus smooth cells impairs O2 constriction contributing to patent ductus arteriosus. Pediatr Res 63:176-181

    Article  PubMed  Google Scholar 

  50. Hong Z, Hong F, Olschewski A et al (2006) Role of store-operated calcium channels and calcium sensitization in normoxic contraction of the ductus arteriosus. Circulation 114:1372-1379

    Article  PubMed  CAS  Google Scholar 

  51. Ward JPT (2006) Hypoxic pulmonary vasoconstriction is mediated by increased production of reactive oxygen species. J Appl Physiol 101:993-995

    Article  PubMed  CAS  Google Scholar 

  52. Weir EK, Archer SL (2006) Hypoxic pulmonary vasoconstriction is/is not mediated by increased production of reactive oxygen species. J Appl Physiol 101:995-998

    Article  PubMed  CAS  Google Scholar 

  53. Weir EK, López-Barneo J, Buckler KJ, Archer SL (2005) Acute oxygen-sensing mechanisms. N Engl J Med 353:2042-2055

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work is supported by NIH RO1 HL 65322 (E.K.W).

Author information

Authors and Affiliations

  1. VA Medical Center, 1 Veterans Drive, 111C, Minneapolis, MN, 55417, USA

    E. Kenneth Weir, Jésus A. Cabrera, Saswati Mahapatra, Douglas A. Peterson & Zhigang Hong

Authors
  1. E. Kenneth Weir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jésus A. Cabrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saswati Mahapatra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Douglas A. Peterson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhigang Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. Kenneth Weir .

Editor information

Editors and Affiliations

  1. Departments of Medicine and Pharmacology, University of Illinois at Chicago, Chicago, 60612, USA

    Jason X. -J. Yuan

  2. Guy’s Hospital Campus, Dept. Physiology, King’s College London, London, SE1 1UL, United Kingdom

    Jeremy P. T. Ward

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this paper

Cite this paper

Weir, E.K., Cabrera, J.A., Mahapatra, S., Peterson, D.A., Hong, Z. (2010). The Role of Ion Channels in Hypoxic Pulmonary Vasoconstriction. In: Yuan, JJ., Ward, J. (eds) Membrane Receptors, Channels and Transporters in Pulmonary Circulation. Advances in Experimental Medicine and Biology, vol 661. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-500-2_1

Download citation

Publish with us

Policies and ethics

Search

Navigation