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Regulation of Ion Channels in Pulmonary Artery Smooth Muscle Cells

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Hypoxic Pulmonary Vasoconstriction

Part of the book series: Developments in Cardiovascular Medicine ((DICM,volume 252))

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Summary

Owning to the development of modern electrophysiological and molecular biology techniques, enormous progress in our understanding of the function, physiological significance and molecular identity of pulmonary ion channels has been made during last two decades since the first recording of the ion channel currents. This work has revealed a complexity and heterogeneity of ion channel expression in PASMCs, which depends on both the species and the site of the arterial vasculature under investigation, as well as multiple potential mechanisms for oxygen sensing by ion channels (24, 56). Therefore, the key questions in pulmonary ion physiology remain essentially the same: how does hypoxia causes HPV, which types of ion channels are involved in this process, and what is the mechanism(s) responsible for the oxygen sensitivity of ion channels involved? Since it is possible that hypoxia may not directly target the ion channels, but may alter their activity via unknown intracellular regulatory factors, the investigation of molecular mechanisms which specifically control the pulmonary ion channels, (particularly those regulating K+ and Ca2+ transport) represents an important and challenging task for the future research in the field of pulmonary electrophysiology.

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References

  1. Albarwani S, Heinert G, Turner JL, and Kozlowski RZ. Differential K+ channel distribution in smooth muscle cells isolated from the pulmonary arterial tree of the rat. Biochem. Biophys. Res. Commun. 1995; 208 183–189.

    Article  CAS  PubMed  Google Scholar 

  2. Archer SL, Huang J, Henry T, Peterson D, and Weir EK. A redox-based O2 sensor in rat pulmonary vasculature. Circ. Res. 1993; 73: 1100–1112.

    CAS  PubMed  Google Scholar 

  3. Archer SL, Huang JMC, Hampl V, Nelson DP, Shultz PJ, and Weir EK. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA. 1994; 91: 7583–7587.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  5. Archer SL, London B, Hampl V, Wu X, Nsair A, Puttagunta L, Hashimoto K, Waite RE, and Michelakis ED. Impairment of hypoxic pulmonary vasoconstriction in mice lacking the voltage-gated potassium channel Kv1.5. FASEB J. 2001; 15: 1801–1803.

    CAS  PubMed  Google Scholar 

  6. Archer SL, Reeve HL, Michelakis E, Puttagunta L, Waite R, Nelson DP, Dinauer MC, and Weir EK. O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase. Proc. Natl. Acad. Sci. USA. 1999; 96: 7944–7949.

    Article  CAS  PubMed  Google Scholar 

  7. Archer SL, and Rusch NJ. Potassium Channels in Cardiovascular Biology. New York, NY: Kluwer Academic/Plenum Press, 2001.

    Google Scholar 

  8. Archer SL, Souil E, Dinh-Xuan AT, Schremmer B, Mercure JV, El Yaagoubi A, Nguyen-Huu L, Reeve HL, and Hampl V. Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes. J. Clin. Invest. 1998; 101: 2319–2330.

    CAS  PubMed  Google Scholar 

  9. Barbé C, Dubuis E, Rochetaing A, Kreher P, Bonnet P, and Vandier C. A 4-AP-sensitive current is enhanced by chronic carbon monoxide exposure in coronary artery myocytes. Am. J. Physiol. Heart Circ. Physiol. 2002; 282: H2031–H2038.

    PubMed  Google Scholar 

  10. Barnes PJ and Liu SF. Regulation of pulmonary vascular tone. Pharmacol. Rev. 1995; 47: 87–131.

    CAS  PubMed  Google Scholar 

  11. Belevych AE, Beck R, Tammaro P, Poston L, and Smirnov SV. Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes. Cardiovasc. Res. 2002; 54: 152–161.

    Article  CAS  PubMed  Google Scholar 

  12. Buryi VA and Gurkovskaia AV. Transmembrane ion currents in pulmonary artery smooth muscle. Biull Eksper Biol. Med. 1980; 90: 519–521.

    CAS  Google Scholar 

  13. Clapp LH and Gurney AM. Modulation of calcium movements by nitroprusside in isolated vascular smooth muscle cells. Pflügers Arch. 1991; 418: 462–470.

    Article  CAS  PubMed  Google Scholar 

  14. Clapp LH and Gurney AM. Outward currents in rabbit pulmonary artery cells dissociated with a new technique. Exp. Physiol. 1991; 76: 677–693.

    CAS  PubMed  Google Scholar 

  15. Clapp LH and Gurney AM. ATP-sensitive K+ channels regulate resting potential of pulmonary arterial smooth muscle cells. Am. J. Physiol. 1992; 262: H916–H920.

    CAS  PubMed  Google Scholar 

  16. Clapp LH, Turner JL, and Kozlowski RZ. Ca2+-activated Cl− currents in pulmonary arterial myocytes. Am. J. Physiol. 1996; 270: H1577–H1584.

    CAS  PubMed  Google Scholar 

  17. Coppock EA, Martens JR, and Tamkun MM. Molecular basis of hypoxia-induced pulmonary vasoconstriction: role of voltage-gated K+ channels. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 281: L1–L12.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. Cui Y, Tran S, Tinker A, and Clapp LH. The molecular composition of KATP channels in human pulmonary artery smooth muscle cells and their modulation by growth. Am. J. Respir. Cell. Mol. Biol. 2002; 26: 135–143.

    CAS  PubMed  Google Scholar 

  20. Duan D, Zhong J, Hermoso M, Satterwhite CM, Rossow CF, Hatton WJ, Yamboliev I, Horowitz B, and Hume JR. Functional inhibition of native volume-sensitive outwardly rectifying anion channels in muscle cells and Xenopus oocytes by anti-ClC-3 antibody. J. Physiol. 2001; 531: 437–444.

    Article  CAS  PubMed  Google Scholar 

  21. Evans AM, Osipenko ON, and Gurney AM. Properties of a novel K+ current that is active at resting potential in rabbit pulmonary artery smooth muscle cells. J. Physiol. 1996; 496: 407–420.

    CAS  PubMed  Google Scholar 

  22. Franco-Obregón A and López-Barneo J. Differential oxygen sensitivity of calcium channels in rabbit smooth muscle cells of conduit and resistance pulmonary arteries. J. Physiol. 1996; 491: 511–518.

    PubMed  Google Scholar 

  23. Gelband CH, Ishikawa T, Post JM, Keef KD, and Hume JR. Intracellular divalent cations block smooth muscle K+ channels. Circ. Res. 1993; 73: 24–34.

    CAS  PubMed  Google Scholar 

  24. Gurney AM. Multiple sites of oxygen sensing and their contributions to hypoxic pulmonary vasoconstriction. Respir. Physiol. Neurobiol. 2002; 132: 43–53.

    Article  CAS  PubMed  Google Scholar 

  25. Gurney AM, Osipenko ON, MacMillan D and Kempsill FE. Potassium channels underlying the resting potential of pulmonary artery smooth muscle cells. Clin. Exp. Pharmacol. Physiol. 2002; 29: 330–333.

    Article  CAS  PubMed  Google Scholar 

  26. Hogg DS, Davies AR, McMurray G, and Kozlowski RZ. KvO2.1 channels mediate hypoxic inhibition of I KV in native pulmonary arterial smooth muscle cells of the rat. Cardiovasc. Res. 2002; 55: 349–360.

    Article  CAS  PubMed  Google Scholar 

  27. Hogg RC, Wang Q, Helliwell RM, and Large WA. Properties of spontaneous inward currents in rabbit pulmonary artery smooth muscle cells. Pflügers Arch. 1993; 425: 233–240.

    Article  CAS  PubMed  Google Scholar 

  28. Hulme JT, Coppock EA, Felipe A, Martens JR, and Tamkun MM. Oxygen sensitivity of cloned voltage-gated K+ channels expressed in the pulmonary vasculature. Circ. Res. 1999; 85: 489–497.

    CAS  PubMed  Google Scholar 

  29. Kirber MT, Ordway RW, Clapp LH, Walsh JV, Jr., and Singer JJ. Both membrane stretch and fatty acids directly activate large conductance Ca2+-activated K+ channels in vascular smooth muscle cells. FEBS Lett. 1992; 297: 24–28.

    Article  CAS  PubMed  Google Scholar 

  30. Kwak Y-G, Navarro-Polanco RA, Grobaski T, Gallagher DJ, and Tamkun MM. Phosphorylation is required for alteration of Kv1.5 K+ channel function by the KOvβ1.3 subunit. J. Biol. Chem. 1999; 274: 25355–25361.

    CAS  PubMed  Google Scholar 

  31. Large WA and Wang Q. Characteristics and physiological role of the Ca2+-activated Cl− conductance in smooth muscle. Am. J. Physiol. 1996; 271: C435–C454.

    CAS  PubMed  Google Scholar 

  32. Mandegar M, Remillard CV, and Yuan J-X. Ion channels in pulmonary arterial hypertension. Prog. Cardiovasc. Dis. 2002; 45: 81–114.

    CAS  PubMed  Google Scholar 

  33. Nelson MT, Patlak JB, Worley JF, and Standen NB. Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone. Am. J. Physiol. 1990; 259: C3–C18.

    CAS  PubMed  Google Scholar 

  34. Osipenko ON, Alexander D, MacLean MR, and Gurney AM. 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. 1998; 124: 1335–1337.

    Article  CAS  PubMed  Google Scholar 

  35. Osipenko ON, Tate RJ, and Gurney AM. Potential role for Kv3.1b channels as oxygen sensors. Circ. Res. 2000; 86: 534–540.

    CAS  PubMed  Google Scholar 

  36. Park MK, Lee SH, Lee SJ, Ho WK, and Earm YE. Different modulation of Ca-activated K channels by the intracellular redox potential in pulmonary and ear arterial smooth muscle cells of the rabbit. Pflügers Arch. 1995; 430: 308–314.

    Article  CAS  PubMed  Google Scholar 

  37. Patel AJ and Honoré E. Molecular physiology of Oxygen-sensitive potassium channels. Eur. Respir. J. 2001; 18: 221–227.

    Article  CAS  PubMed  Google Scholar 

  38. Patel AJ, Lazdunski M, and Honoré E. Kv2.1/Kv9.3, a novel ATP-dependent delayed-rectifier K+ channel in oxygen-sensitive pulmonary artery myocytes. EMBO J. 1997; 16: 6615–6625.

    Article  CAS  PubMed  Google Scholar 

  39. Peng W, Hoidal JR, Karwande SV, and Farrukh IS. Effect of chronic hypoxia on K+ channels: regulation in human pulmonary vascular smooth muscle cells. Am. J. Physiol. 1997; 272: C1271–C1278.

    CAS  PubMed  Google Scholar 

  40. Platoshyn O, Yu Y, Golovina VA, McDaniel SS, Krick S, Li L, Wang JY, Rubin LJ, and Yuan JX-J. Chronic hypoxia decreases Kv channel expression and function in pulmonary artery myocytes. Am. J. Physiol. Lung Cell. Mol. Physiol. 2001; 280: L801–L812.

    CAS  PubMed  Google Scholar 

  41. Post JM, Hume JR, Archer SL, and Weir EK. Direct role for potassium channel inhibition in hypoxic pulmonary vasoconstriction. Am. J. Physiol. 1992; 262: C882–C890.

    CAS  PubMed  Google Scholar 

  42. Reeve HL, Michelakis E, Nelson DP, Weir EK, and Archer SL. Alterations in a redox oxygen sensing mechanism in chronic hypoxia. J. Appl. Physiol. 2001; 90: 2249–2256.

    CAS  PubMed  Google Scholar 

  43. Salter KJ and Kozlowski RZ. Endothelin receptor coupling to potassium and chloride channels in isolated rat pulmonary arterial myocytes. J. Pharmacol. Exp. Ther. 1996; 279: 1053–1062.

    CAS  PubMed  Google Scholar 

  44. Salter KJ, Turner JL, Albarwani S, Clapp LH, and Kozlowski RZ. Ca2+-activated Cl− and K+ channels and their modulation by endothelin-1 in rat pulmonary arterial smooth muscle cells. Exp. Physiol. 1995; 80: 815–824.

    CAS  PubMed  Google Scholar 

  45. Shimoda LA, Sylvester JT, and Sham JSK. Inhibition of voltage-gated K+ current in rat intrapulmonary arterial myocytes by endothelin-1. Am. J. Physiol. Lung Cell. Mol. Physiol. 1998; 274: L842–L853.

    CAS  Google Scholar 

  46. Shimoda LA, Sylvester JT, and Sham JSK. Chronic hypoxia alters effects of endothelin and angiotensin on K+ currents in pulmonary arterial myocytes. Am. J. Physiol. Lung Cell. Mol. Physiol. 1999; 277: L431–L439.

    CAS  Google Scholar 

  47. Smani T, Iwabuchi S, López-Barneo J, and Ureña J. Differential segmental activation of Ca2+-dependent Cl− and K+ channels in pulmonary arterial myocytes. Cell Calcium. 2001; 29: 369–377.

    Article  CAS  PubMed  Google Scholar 

  48. Smirnov SV and Aaronson PI. Alteration of the transmembrane K+ gradient during development of delayed rectifier in isolated rat pulmonary arterial cells. J. Gen. Physiol. 1994; 104: 241–264.

    Article  CAS  PubMed  Google Scholar 

  49. Smirnov SV and Aaronson PI. Inhibition of vascular smooth muscle cell K+ currents by tyrosine kinase inhibitors genistein and ST 638. Circ. Res. 1995; 76: 310–316.

    CAS  PubMed  Google Scholar 

  50. Smirnov SV and Aaronson PI. Modulatory effects of arachidonic acid on the delayed rectifier K+ current in rat pulmonary arterial myocytes. Structural aspects and involvement of protein kinase C. Circ. Res. 1996; 79: 20–31.

    CAS  PubMed  Google Scholar 

  51. Smirnov SV, Beck R, Tammaro P, Ishii T, and Aaronson PI. Electrophysiologically distinct smooth muscle cell subtypes in rat conduit and resistance pulmonary arteries. J. Physiol. 2002; 538: 867–878.

    Article  CAS  PubMed  Google Scholar 

  52. Smirnov SV, Knock GA, and Aaronson PI. Effects of the 5-lipoxygenase activating protein inhibitor MK886 on voltage-gated and Ca2+-activated K+ currents in rat arterial myocytes. Br. J. Pharmacol. 1998; 124: 572–578.

    Article  CAS  PubMed  Google Scholar 

  53. Smirnov SV, Robertson TP, Ward JPT, and Aaronson PI. Chronic hypoxia is associated with reduced delayed rectifier K+ current in rat pulmonary artery muscle cells. Am. J. Physiol. 1994; 266: H365–H370.

    CAS  PubMed  Google Scholar 

  54. Standen NB and Quayle JM. K+ channel modulation in arterial smooth muscle. Acta Physiol. Scand. 1998; 164: 549–557.

    Article  CAS  PubMed  Google Scholar 

  55. Thuringer D and Findlay I. Contrasting effects of intracellular redox couples on the regulation of maxi-K channels in isolated myocytes from rabbit pulmonary artery. J. Physiol. 1997; 500: 583–592.

    CAS  PubMed  Google Scholar 

  56. Ward JP and Aaronson PI. Mechanisms of hypoxic pulmonary vasoconstriction: can anyone be right? Respir. Physiol. 1999; 115: 261–271.

    Article  CAS  PubMed  Google Scholar 

  57. Weir EK and Archer SL. The mechanism of acute hypoxic pulmonary vasoconstriction: the tale of two channels. FASEB J. 1995; 9: 183–189.

    CAS  PubMed  Google Scholar 

  58. Yamazaki J, Duan D, Janiak R, Kuenzli K, Horowitz B, and Hume JR. Functional and molecular expression of volume-regulated chloride channels in canine vascular smooth muscle cells. J. Physiol. 1998; 507: 729–736.

    Article  CAS  PubMed  Google Scholar 

  59. Yuan X-J. Voltage-gated K+ currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes. Circ. Res. 1995; 77: 370–378.

    CAS  PubMed  Google Scholar 

  60. Yuan X-J. Role of calcium-activated chloride current in regulating pulmonary vasomotor tone. Am. J. Physiol. 1997; 272: L959–L968.

    CAS  PubMed  Google Scholar 

  61. Yuan X-J, Sugiyama T, Goldman WF, Rubin LJ, and Blaustein MP. A mitochondrial uncoupler increases KCa currents but decreases Kv currents in pulmonary artery myocytes. Am. J. Physiol. 1996; 270: C321–C331.

    CAS  PubMed  Google Scholar 

  62. Yuan X-J, Tod ML, Rubin LJ, and Blaustein MP. Deoxyglucose and reduced glutathione mimic effects of hypoxia on K+ and Ca2+ conductances in pulmonary artery cells. Am. J. Physiol. 1994; 267: L52–L63.

    CAS  PubMed  Google Scholar 

  63. Yuan X-J, Tod ML, Rubin LJ, and Blaustein MP. Inhibition of cytochrome P-450 reduces voltage-gated K+ currents in pulmonary arterial myocytes. Am. J. Physiol. 1995; 268: C259–C270.

    CAS  PubMed  Google Scholar 

  64. Yuan X-J, Tod ML, Rubin LJ, and Blaustein MP. NO hyperpolarizes pulmonary artery smooth muscle cells and decreases the intracellular Ca2+ concentration by activating voltagegated K+ channels. Proc. Natl. Acad. Sci. USA. 1996; 93: 10489–10494.

    CAS  PubMed  Google Scholar 

  65. Yuan X-J, Wang J, Juhaszova M, Golovina VA, and Rubin LJ. Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 1998; 274: L621–L635.

    CAS  Google Scholar 

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Smirnov, S.V. (2004). Regulation of Ion Channels in Pulmonary Artery Smooth Muscle Cells. In: Yuan, J.X.J. (eds) Hypoxic Pulmonary Vasoconstriction. Developments in Cardiovascular Medicine, vol 252. Springer, Boston, MA. https://doi.org/10.1007/1-4020-7858-7_8

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