title: Liquid movement across the surface epithelium of large airways.
abstract: The cystic fibrosis transmembrane conductance regulator CFTR gene is found on chromosome 7 [Kerem, B., Rommens, J.M., Buchanan, J.A., Markiewicz, D., Cox, T.K., Chakravarti, A., Buchwald, M., Tsui, L.C., 1989. Identification of the cystic fibrosis gene: genetic analysis. Science 245, 1073-1080; Riordan, J.R., Rommens, J.M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.L., et al., 1989. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073] and encodes for a 1480 amino acid protein which is present in the plasma membrane of epithelial cells [Anderson, M.P., Sheppard, D.N., Berger, H.A., Welsh, M.J., 1992. Chloride channels in the apical membrane of normal and cystic fibrosis airway and intestinal epithelia. Am. J. Physiol. 263, L1-L14]. This protein appears to have many functions, but a unifying theme is that it acts as a protein kinase C- and cyclic AMP-regulated Cl(-) channel [Winpenny, J.P., McAlroy, H.L., Gray, M.A., Argent, B.E., 1995. Protein kinase C regulates the magnitude and stability of CFTR currents in pancreatic duct cells. Am. J. Physiol. 268, C823-C828; Jia, Y., Mathews, C.J., Hanrahan, J.W., 1997. Phosphorylation by protein kinase C is required for acute activation of cystic fibrosis transmembrane conductance regulator by protein kinase A. J. Biol. Chem. 272, 4978-4984]. In the superficial epithelium of the conducting airways, CFTR is involved in Cl(-) secretion [Boucher, R.C., 2003. Regulation of airway surface liquid volume by human airway epithelia. Pflugers Arch. 445, 495-498] and also acts as a regulator of the epithelial Na(+) channel (ENaC) and hence Na(+) absorption [Boucher, R.C., Stutts, M.J., Knowles, M.R., Cantley, L., Gatzy, J.T., 1986. Na(+) transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation. J. Clin. Invest. 78, 1245-1252; Stutts, M.J., Canessa, C.M., Olsen, J.C., Hamrick, M., Cohn, J.A., Rossier, B.C., Boucher, R.C., 1995. CFTR as a cAMP-dependent regulator of sodium channels. Science 269, 847-850]. In this chapter, we will discuss the regulation of these two ion channels, and how they can influence liquid movement across the superficial airway epithelium.
authors: Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA.
authors: Lucy A
authors: LA
authors: Chambers
authors: Brett M
authors: BM
authors: Rollins
authors: Robert
authors: R
authors: Tarran
mesh_terms: D000818:Animals; D001825:Body Fluid Compartments / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D009093:Mucus / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D002712:Chlorides; D053503:Epithelial Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium; D000242:Cyclic AMP
references: Eur J Morphol. 1998 Aug;36 Suppl:67-73
references: 9825896
references: Cell. 1998 Dec 23;95(7):1005-15
references: 9875854
references: J Membr Biol. 2004 Nov;202(1):21-37
references: 15702377
references: Pediatr Radiol. 2005 Aug;35(8):739-57
references: 15868140
references: Am J Respir Cell Mol Biol. 2000 Dec;23(6):755-61
references: 11104728
references: J Biol Chem. 2003 Mar 28;278(13):11256-64
references: 12551890
references: J Physiol. 2003 Jun 15;549(Pt 3):845-53
references: 12702745
references: Paediatr Respir Rev. 2003 Sep;4(3):172-7
references: 12880751
references: Respir Res. 2003;4:8
references: 14511398
references: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16083-8
references: 14668433
references: J Physiol. 2004 Apr 1;556(Pt 1):1-10
references: 14660706
references: Nat Med. 2004 May;10(5):487-93
references: 15077107
references: J Biol Chem. 2004 May 7;279(19):20234-41
references: 14993227
references: J Biol Chem. 2004 Aug 27;279(35):36855-64
references: 15210701
references: J Biol Chem. 2004 Sep 10;279(37):38854-60
references: 15234967
references: Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L928-35
references: 15246975
references: J Clin Invest. 1983 May;71(5):1410-7
references: 6853720
references: Science. 1983 Sep 9;221(4615):1067-70
references: 6308769
references: Am Rev Respir Dis. 1983 Aug;128(2 Pt 2):S14-20
references: 6881701
references: J Clin Invest. 1986 Nov;78(5):1245-52
references: 3771796
references: Am J Physiol. 1989 May;256(5 Pt 1):C1033-44
references: 2719093
references: Am J Physiol. 1989 May;256(5 Pt 1):C1045-53
references: 2719094
references: Am J Physiol. 1989 May;256(5 Pt 1):C1054-63
references: 2719095
references: Science. 1989 Sep 8;245(4922):1066-73
references: 2475911
references: Science. 1989 Sep 8;245(4922):1073-80
references: 2570460
references: Clin Microbiol Rev. 1991 Jan;4(1):35-51
references: 1900735
references: Am J Physiol. 1991 Aug;261(2 Pt 1):C319-31
references: 1872374
references: Am J Physiol. 1991 Aug;261(2 Pt 1):C332-41
references: 1872375
references: Br J Pharmacol. 1991 Jul;103(3):1649-56
references: 1718521
references: Am J Physiol. 1992 Jul;263(1 Pt 1):L1-14
references: 1322048
references: Mol Med. 2000 Nov;6(11):969-82
references: 11147574
references: Biophys J. 2001 May;80(5):2176-86
references: 11325720
references: News Physiol Sci. 2001 Feb;16:1-5
references: 11390937
references: Am J Physiol Lung Cell Mol Physiol. 2001 Jul;281(1):L16-23
references: 11404240
references: J Gen Physiol. 2001 Aug;118(2):223-36
references: 11479349
references: Am J Respir Crit Care Med. 2001 Aug 1;164(3):443-6
references: 11500347
references: Mol Cell. 2001 Jul;8(1):149-58
references: 11511368
references: Am J Physiol Cell Physiol. 2001 Dec;281(6):C1991-2002
references: 11698258
references: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):14120-5
references: 11707576
references: J Biol Chem. 2002 Mar 8;277(10):8338-45
references: 11756432
references: J Clin Invest. 2002 Mar;109(5):571-7
references: 11877463
references: Methods Mol Med. 2002;70:479-92
references: 11917544
references: Cochrane Database Syst Rev. 2002;(2):CD002768
references: 12076449
references: Am J Physiol Lung Cell Mol Physiol. 2002 Aug;283(2):L329-35
references: 12114194
references: J Pharmacol Exp Ther. 2002 Sep;302(3):871-80
references: 12183642
references: J Gen Physiol. 2002 Sep;120(3):407-18
references: 12198094
references: J Physiol. 2002 Nov 15;545(Pt 1):199-206
references: 12433960
references: J Clin Invest. 2002 Dec;110(11):1651-8
references: 12464670
references: Pflugers Arch. 2003 Jan;445(4):495-8
references: 12548395
references: Proc Am Thorac Soc. 2004;1(1):4-9
references: 16113404
references: Proc Am Thorac Soc. 2004;1(1):33-7
references: 16113409
references: Proc Am Thorac Soc. 2004;1(1):47-53
references: 16113412
references: Pediatr Pulmonol. 2005 Oct;40(4):279-84
references: 15858812
references: J Biol Chem. 2005 Sep 9;280(36):31587-94
references: 16027156
references: J Biol Chem. 2005 Oct 21;280(42):35751-9
references: 16087672
references: N Engl J Med. 2006 Jan 19;354(3):241-50
references: 16421365
references: Annu Rev Physiol. 2006;68:543-61
references: 16460283
references: Am J Respir Crit Care Med. 2006 Mar 1;173(5):475-82
references: 16126935
references: J Gen Physiol. 2006 May;127(5):591-604
references: 16636206
references: Novartis Found Symp. 2006;276:26-48; discussion 48-57, 275-81
references: 16805422
references: Br J Pharmacol. 2006 Sep;149(1):43-55
references: 16880767
references: J Biol Chem. 2006 Sep 22;281(38):27942-9
references: 16873367
references: Curr Opin Pulm Med. 2006 Nov;12(6):445-52
references: 17053496
references: Am J Physiol Cell Physiol. 2006 Dec;291(6):C1258-70
references: 16822939
references: J Intern Med. 2007 Jan;261(1):5-16
references: 17222164
references: Biochim Biophys Acta. 2007 Apr;1773(4):476-9
references: 17306384
references: Am J Physiol Cell Physiol. 2007 Apr;292(4):C1553-61
references: 17182731
references: Am J Physiol Lung Cell Mol Physiol. 2007 Jun;292(6):L1432-43
references: 17322286
references: J Cyst Fibros. 2007 Nov 30;6(6):419-22
references: 17434346
references: Nature. 1999 Nov 18;402(6759):301-4
references: 10580502
references: J Pediatr. 2000 Mar;136(3):304-10
references: 10700685
references: J Am Soc Nephrol. 2000 May;11(5):828-34
references: 10770960
references: J Clin Invest. 2000 May;105(10):1419-27
references: 10811849
references: J Biol Chem. 2000 Sep 8;275(36):27947-56
references: 10821834
references: Am J Physiol. 1993 Mar;264(3 Pt 1):C591-602
references: 7681623
references: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):479-83
references: 7507247
references: Am J Respir Crit Care Med. 1994 Jul;150(1):271-81
references: 8025763
references: Am J Physiol. 1994 Jul;267(1 Pt 1):C293-300
references: 8048488
references: Thorax. 1994 Dec;49(12):1249-50
references: 7878563
references: Am J Physiol. 1995 Apr;268(4 Pt 1):C823-8
references: 7537451
references: Science. 1995 Aug 11;269(5225):847-50
references: 7543698
references: FEBS Lett. 1997 Jan 6;400(3):341-4
references: 9009227
references: J Biol Chem. 1997 Feb 21;272(8):4978-84
references: 9030559
references: Am J Physiol. 1997 Apr;272(4 Pt 1):C1077-86
references: 9142832
references: Nature. 1997 Oct 9;389(6651):607-10
references: 9335501
references: Am J Physiol. 1997 Nov;273(5 Pt 1):L1036-41
references: 9374732
references: J Gen Physiol. 1998 Jan;111(1):127-38
references: 9417140
references: Am J Physiol. 1998 Mar;274(3 Pt 1):L388-95
references: 9530174
references: J Biol Chem. 1998 May 29;273(22):14053-8
references: 9593757