|
|
||||||||
Departments of 1 Pediatrics and 2 Physiology and 3 Center for Cell and Molecular Signaling, Emory University School of Medicine, Atlanta, Georgia 30322
Alveolar fluid
clearance in the developing and mature lungs is believed to be mediated
by some form of epithelial Na channels (ENaC). However, single-channel
studies using isolated alveolar type II (ATII) cells have failed to
demonstrate consistently the presence of highly selective
Na+ channels that would be expected from ENaC expression.
We postulated that in vitro culture conditions might be responsible for
alterations in the biophysical properties of Na+
conductances observed in cultured ATII cells. When ATII cells were
grown on glass plates submerged in media that lacked steroids, the
predominant channel was a 21-pS nonselective cation channel (NSC) with
a Na+-to-K+ selectivity of 1; however, when
grown on permeable supports in the presence of steroids and air
interface, the predominant channel was a low-conductance (6.6 ± 3.4 pS, n = 94), highly Na+-selective
channel (HSC) with a
PNa/PK >80 that is
inhibited by submicromolar concentrations of amiloride
(K0.5 = 37 nM) and is similar in
biophysical properties to ENaC channels described in other epithelia.
To establish the relationship of this HSC channel to the cloned ENaC,
we employed antisense oligonucleotide methods to inhibit the individual
subunit proteins of ENaC (
,
, and
) and used patch-clamp
techniques to determine the density of this channel in apical membrane
patches of ATII cells. Overnight treatment of cells with antisense
oligonucleotides to any of the three subunits of ENaC resulted in a
significant decrease in the density of HSC channels in the apical
membrane cell-attached patches. Taken together, these results show that
when grown on permeable supports in the presence of steroids and air
interface, the predominant channels expressed in ATII cells have
single-channel characteristics resembling channels that are associated
with the coexpression of the three cloned ENaC subunits
-,
-, and
-ENaC.
single-channel recording; air interface; antisense oligonucleotides; epithelial sodium channels
This article has been cited by other articles:
![]() |
K. B. Adler and S. Matalon Highlights of the December Issue Am. J. Respir. Cell Mol. Biol., December 1, 2009; 41(6): 629 - 630. [Full Text] [PDF] |
||||
![]() |
A. Lazrak, K. E. Iles, G. Liu, D. L. Noah, J. W. Noah, and S. Matalon Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species FASEB J, November 1, 2009; 23(11): 3829 - 3842. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Johnson, L. Allen, and L. Dobbs Characteristics of Cl- uptake in rat alveolar type I cells Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L816 - L827. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Yang, L. Su, Y. Wang, and L. Liu UTP regulation of ion transport in alveolar epithelial cells involves distinct mechanisms Am J Physiol Lung Cell Mol Physiol, September 1, 2009; 297(3): L439 - L454. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. M. Jesse, J. McCartney, X. Feng, E. M. Richards, C. E. Wood, and M. Keller-Wood Expression of ENaC subunits, chloride channels, and aquaporins in ovine fetal lung: ontogeny of expression and effects of altered fetal cortisol concentrations Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R453 - R461. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Gallacher, S. G. Brown, B. G. Hale, R. Fearns, R. E. Olver, R. E. Randall, and S. M. Wilson Cation currents in human airway epithelial cells induced by infection with influenza A virus J. Physiol., July 1, 2009; 587(13): 3159 - 3173. [Abstract] [Full Text] [PDF] |
||||
![]() |
H.-L. Ji, W. Song, Z. Gao, X.-F. Su, H.-G. Nie, Y. Jiang, J.-B. Peng, Y.-X. He, Y. Liao, Y.-J. Zhou, et al. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L372 - L383. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Caci, R. Melani, N. Pedemonte, G. Yueksekdag, R. Ravazzolo, J. Rosenecker, L. J. V. Galietta, and O. Zegarra-Moran Epithelial Sodium Channel Inhibition in Primary Human Bronchial Epithelia by Transfected siRNA Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 211 - 216. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. P. Albert, A. M. Woollhead, O. J. Mace, and D. L. Baines AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers Am J Physiol Lung Cell Mol Physiol, November 1, 2008; 295(5): L837 - L848. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. G. Brown, M. Gallacher, R. E. Olver, and S. M. Wilson The regulation of selective and nonselective Na+ conductances in H441 human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L942 - L954. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Randrianarison, C. Clerici, C. Ferreira, A. Fontayne, S. Pradervand, N. Fowler-Jaeger, E. Hummler, B. C. Rossier, and C. Planes Low expression of the {beta}-ENaC subunit impairs lung fluid clearance in the mouse Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L409 - L416. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. O'Brodovich, P. Yang, S. Gandhi, and G. Otulakowski Amiloride-insensitive Na+ and fluid absorption in the mammalian distal lung Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L401 - L408. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Yu, H.-F. Bao, J. L. Self, D. C. Eaton, and M. N. Helms Aldosterone-induced increases in superoxide production counters nitric oxide inhibition of epithelial Na channel activity in A6 distal nephron cells Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1666 - F1677. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Otulakowski, W. Duan, S. Gandhi, and H. O'Brodovich Steroid and Oxygen Effects on eIF4F Complex, mTOR, and ENaC Translation in Fetal Lung Epithelia Am. J. Respir. Cell Mol. Biol., October 1, 2007; 37(4): 457 - 466. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Song and S. Matalon Modulation of alveolar fluid clearance by reactive oxygen-nitrogen intermediates Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L855 - L858. [Full Text] [PDF] |
||||
![]() |
N. Randrianarison, B. Escoubet, C. Ferreira, A. Fontayne, N. Fowler-Jaeger, C. Clerici, E. Hummler, B. C. Rossier, and C. Planes beta-Liddle mutation of the epithelial sodium channel increases alveolar fluid clearance and reduces the severity of hydrostatic pulmonary oedema in mice J. Physiol., July 15, 2007; 582(2): 777 - 788. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Dagenais, R. Frechette, M.-E. Clermont, C. Masse, A. Prive, E. Brochiero, and Y. Berthiaume Dexamethasone inhibits the action of TNF on ENaC expression and activity Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1220 - L1231. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Leroy, A. Prive, J.-C. Bourret, Y. Berthiaume, P. Ferraro, and E. Brochiero Regulation of ENaC and CFTR expression with K+ channel modulators and effect on fluid absorption across alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, December 1, 2006; 291(6): L1207 - L1219. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. N. Helms, J. Self, H. F. Bao, L. C. Job, L. Jain, and D. C. Eaton Dopamine activates amiloride-sensitive sodium channels in alveolar type I cells in lung slice preparations Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L610 - L618. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Jain and D. C. Eaton Alveolar fluid transport: a changing paradigm Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L646 - L648. [Full Text] [PDF] |
||||
![]() |
X. Su, L. Robriquet, H. G. Folkesson, and M. A. Matthay Protective effect of endogenous beta-adrenergic tone on lung fluid balance in acute bacterial pneumonia in mice Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L769 - L776. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. N. Helms, X.-J. Chen, S. Ramosevac, D. C. Eaton, and L. Jain Dopamine regulation of amiloride-sensitive sodium channels in lung cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L710 - L722. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Otulakowski, B. Rafii, M. Harris, and H. O'Brodovich Oxygen and Glucocorticoids Modulate {alpha}ENaC mRNA Translation in Fetal Distal Lung Epithelium Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 204 - 212. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Fang, Y. Song, J. Hirsch, L. J. V. Galietta, N. Pedemonte, R. L. Zemans, G. Dolganov, A. S. Verkman, and M. A. Matthay Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L242 - L249. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M. Mutlu and J. I. Sznajder Mechanisms of pulmonary edema clearance Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L685 - L695. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Looney, C. Sartori, S. Chakraborty, P. F. James, J. B. Lingrel, and M. A. Matthay Decreased expression of both the {alpha}1- and {alpha}2-subunits of the Na-K-ATPase reduces maximal alveolar epithelial fluid clearance Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L104 - L110. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Mair, M. Frick, C. Bertocchi, T. Haller, A. Amberger, H. Weiss, R. Margreiter, W. Streif, and P. Dietl Inhibition by cytoplasmic nucleotides of a new cation channel in freshly isolated human and rat type II pneumocytes Am J Physiol Lung Cell Mol Physiol, December 1, 2004; 287(6): L1284 - L1292. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S. Awayda, A. Bengrine, N. A. Tobey, J. D. Stockand, and R. C. Orlando Nonselective cation transport in native esophageal epithelia Am J Physiol Cell Physiol, August 1, 2004; 287(2): C395 - C402. [Abstract] [Full Text] [PDF] |
||||
![]() |
X.-J. Chen, S. Seth, G. Yue, P. Kamat, R. W. Compans, D. Guidot, L. A. Brown, D. C. Eaton, and L. Jain Influenza virus inhibits ENaC and lung fluid clearance Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L366 - L373. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Brochiero, A. Dagenais, A. Prive, Y. Berthiaume, and R. Grygorczyk Evidence of a functional CFTR Cl- channel in adult alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L382 - L392. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. J. Ramminger, K. Richard, S. K. Inglis, S. C. Land, R. E. Olver, and S. M. Wilson A regulated apical Na+ conductance in dexamethasone-treated H441 airway epithelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2004; 287(2): L411 - L419. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Fang, Y. Song, R. Zemans, J. Hirsch, and M. A. Matthay Fluid transport across cultured rat alveolar epithelial cells: a novel in vitro system Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L104 - L110. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Clunes, A. G. Butt, and S. M. Wilson A glucocorticoid-induced Na+ conductance in human airway epithelial cells identified by perforated patch recording J. Physiol., June 15, 2004; 557(3): 809 - 819. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. Hardiman, C. M. McNicholas-Bevensee, J. Fortenberry, C. T. Myles, B. Malik, D. C. Eaton, and S. Matalon Regulation of Amiloride-Sensitive Na+ Transport by Basal Nitric Oxide Am. J. Respir. Cell Mol. Biol., May 1, 2004; 30(5): 720 - 728. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Leroy, A. Dagenais, Y. Berthiaume, and E. Brochiero Molecular identity and function in transepithelial transport of KATP channels in alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2004; 286(5): L1027 - L1037. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Eaton, J. Chen, S. Ramosevac, S. Matalon, and L. Jain Regulation of Na+ Channels in Lung Alveolar Type II Epithelial Cells Proceedings of the ATS, January 1, 2004; 1(1): 10 - 16. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Matalon, K. M. Hardiman, L. Jain, D. C. Eaton, M. Kotlikoff, J. P. Eu, J. Sun, G. Meissner, and J. S. Stamler Regulation of ion channel structure and function by reactive oxygen-nitrogen species Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1184 - L1189. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. C. Willis, K.-J. Kim, X. Li, J. Liebler, E. D. Crandall, and Z. Borok Modulation of ion conductance and active transport by TGF-{beta}1 in alveolar epithelial cell monolayers Am J Physiol Lung Cell Mol Physiol, December 1, 2003; 285(6): L1192 - L1200. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. Kelly, C. Lin, M. Ramkumar, N. C. Saxena, T. R. Kleyman, and D. C. Eaton Characterization of an amiloride binding region in the {alpha}-subunit of ENaC Am J Physiol Renal Physiol, December 1, 2003; 285(6): F1279 - F1290. [Abstract] [Full Text] |
||||
![]() |
O. A. Weisz and J. P. Johnson Noncoordinate regulation of ENaC: paradigm lost? Am J Physiol Renal Physiol, November 1, 2003; 285(5): F833 - F842. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Berthiaume Long-term stimulation of alveolar epithelial cells by {beta}-adrenergic agonists: increased Na+ transport and modulation of cell growth? Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L798 - L801. [Full Text] [PDF] |
||||
![]() |
A. Lazrak and S. Matalon cAMP-induced changes of apical membrane potentials of confluent H441 monolayers Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L443 - L450. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. P. Mason, M. Petersen, C. Melot, B. Imanow, O. Matveykine, M.-T. Gautier, A. Sarybaev, A. Aldashev, M. M. Mirrakhimov, B. H. Brown, et al. Serial changes in nasal potential difference and lung electrical impedance tomography at high altitude J Appl Physiol, May 1, 2003; 94(5): 2043 - 2050. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. O'Grady and S. Y. Lee Chloride and potassium channel function in alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 2003; 284(5): L689 - L700. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Matalon and I. C. Davis Vectorial Sodium Transport Across the Mammalian Alveolar Epithelium: It Occurs but Through Which Cells? Circ. Res., March 7, 2003; 92(4): 348 - 349. [Full Text] [PDF] |
||||
![]() |
U. H. Thome, I. C. Davis, S. V. Nguyen, B. J. Shelton, and S. Matalon Modulation of sodium transport in fetal alveolar epithelial cells by oxygen and corticosterone Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L376 - L385. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Jiang, Y. Song, C. Bai, B. H. Koller, M. A. Matthay, and A. S. Verkman Pleural surface fluorescence measurement of Na+ and Cl- transport across the air space-capillary barrier J Appl Physiol, January 1, 2003; 94(1): 343 - 352. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Matalon, A. Lazrak, L. Jain, and D. C. Eaton Lung Edema Clearance: 20 Years of Progress: Invited Review: Biophysical properties of sodium channels in lung alveolar epithelial cells J Appl Physiol, November 1, 2002; 93(5): 1852 - 1859. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Olivier, U. Scherrer, J.-D. Horisberger, B. C. Rossier, and E. Hummler Lung Edema Clearance: 20 Years of Progress: Selected Contribution: Limiting Na+ transport rate in airway epithelia from alpha -ENaC transgenic mice: a model for pulmonary edema J Appl Physiol, November 1, 2002; 93(5): 1881 - 1887. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Becchetti, B. Malik, G. Yue, P. Duchatelle, O. Al-Khalili, T. R. Kleyman, and D. C. Eaton Phosphatase inhibitors increase the open probability of ENaC in A6 cells Am J Physiol Renal Physiol, November 1, 2002; 283(5): F1030 - F1045. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. D. Crandall and R. M. Effros Lung Edema Clearance: 20 Years of Progress: Historical perspectives on lung edema clearance J Appl Physiol, October 1, 2002; 93(4): 1527 - 1532. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Matthay, C. Clerici, and G. Saumon Lung Edema Clearance: 20 Years of Progress: Invited Review: Active fluid clearance from the distal air spaces of the lung J Appl Physiol, October 1, 2002; 93(4): 1533 - 1541. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. M. Barker and R. E. Olver Lung Edema Clearance: 20 Years of Progress: Invited Review: Clearance of lung liquid during the perinatal period J Appl Physiol, October 1, 2002; 93(4): 1542 - 1548. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Matthay, H. G. Folkesson, and C. Clerici Lung Epithelial Fluid Transport and the Resolution of Pulmonary Edema Physiol Rev, July 1, 2002; 82(3): 569 - 600. [Abstract] [Full Text] [PDF] |
||||
![]() |
O. A. Itani, S. D. Auerbach, R. F. Husted, K. A. Volk, S. Ageloff, M. A. Knepper, J. B. Stokes, and C. P. Thomas Alveolar Epithelial Ion and Fluid Transport: Glucocorticoid-stimulated lung epithelial Na+ transport is associated with regulated ENaC and sgk1 expression Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L631 - L641. [Abstract] [Full Text] [PDF] |
||||
![]() |
X.-J. Chen, D. C. Eaton, and L. Jain Alveolar Epithelial Ion and Fluid Transport: beta -Adrenergic regulation of amiloride-sensitive lung sodium channels Am J Physiol Lung Cell Mol Physiol, April 1, 2002; 282(4): L609 - L620. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |