Liquid movement across the surface epithelium of large airways.
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.
Chambers
Lucy A
LA
Cystic Fibrosis/Pulmonary Research & Treatment Center, University of North Carolina, Chapel Hill, NC 27599-7248, USA.
Rollins
Brett M
BM
Tarran
Robert
R
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*
D002712:Chlorides; D053503:Epithelial Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium; D000242:Cyclic AMP
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