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Physiol. Rev. 77: 359-396, 1997;
0031-9333/97 $15.00
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Physiological Reviews, Vol 77, 359-396, Copyright © 1997 by American Physiological Society

JOURNAL ARTICLE

Epithelial sodium channels: function, structure, and regulation

H. Garty and L. G. Palmer
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.

The apical (outward-facing) membranes of high-resistance epithelia contain Na+ channels, traditionally identified by their sensitivity to block by the K(+)-sparing diuretic amiloride. Such channels have been characterized in amphibian skin and urinary bladder, renal collecting duct, distal colon, sweat and salivary glands, lung, and taste buds. They mediate the first step of active Na+ reabsorption and play a major role in the maintenance of electrolyte and water homeostasis in all vertebrates. In the past, these channels were classified according to their biophysical and pharmacological properties. The recent cloning of the three homologous channel subunits denoted alpha-, beta-, and gamma-epithelial Na+ channels (ENaC) has provided a molecular definition of at least one class of amiloride-blockable channels. Subsequent studies have established that ENaC is a major Na(+)-conducting pathway in both absorbing and secretory epithelia and is related to one type of channel involved in mechanosensation. This review summarizes the biophysical characteristics, molecular properties, and regulatory mechanisms of epithelial amiloride-blockable Na+ channels. Special emphasis is given to recent studies utilizing cloned ENaC subunits and purified amiloride-binding proteins.


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J. Biol. Chem., September 8, 2006; 281(36): 26520 - 26527.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
V. Bhalla, N. M. Oyster, A. C. Fitch, M. A. Wijngaarden, D. Neumann, U. Schlattner, D. Pearce, and K. R. Hallows
AMP-activated Kinase Inhibits the Epithelial Na+ Channel through Functional Regulation of the Ubiquitin Ligase Nedd4-2
J. Biol. Chem., September 8, 2006; 281(36): 26159 - 26169.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
Z. Ergonul, G. Frindt, and L. G. Palmer
Regulation of maturation and processing of ENaC subunits in the rat kidney
Am J Physiol Renal Physiol, September 1, 2006; 291(3): F683 - F693.
[Abstract] [Full Text] [PDF]

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 J. Physiol.Home page
A. Anantharam, Y. Tian, and L. G. Palmer
Open probability of the epithelial sodium channel is regulated by intracellular sodium
J. Physiol., July 15, 2006; 574(2): 333 - 347.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
X. R. Cao, P. P. Shi, R. D. Sigmund, R. F. Husted, C. D. Sigmund, R. A. Williamson, J. B. Stokes, and B. Yang
Mice heterozygous for beta-ENaC deletion have defective potassium excretion
Am J Physiol Renal Physiol, July 1, 2006; 291(1): F107 - F115.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
B. Malik, S. R. Price, W. E. Mitch, Q. Yue, and D. C. Eaton
Regulation of epithelial sodium channels by the ubiquitin-proteasome proteolytic pathway
Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1285 - F1294.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
S. Sheng, M. D. Carattino, J. B. Bruns, R. P. Hughey, and T. R. Kleyman
Furin cleavage activates the epithelial Na+ channel by relieving Na+ self-inhibition
Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1488 - F1496.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
O. Pochynyuk, Q. Tong, A. Staruschenko, H.-P. Ma, and J. D. Stockand
Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides
Am J Physiol Renal Physiol, May 1, 2006; 290(5): F949 - F957.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
Y. Wei, P. Sun, Z. Wang, B. Yang, M. A. Carroll, and W.-H. Wang
Adenosine inhibits ENaC via cytochrome P-450 epoxygenase-dependent metabolites of arachidonic acid
Am J Physiol Renal Physiol, May 1, 2006; 290(5): F1163 - F1168.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
L.-M. Yang, R. Rinke, and C. Korbmacher
Stimulation of the Epithelial Sodium Channel (ENaC) by cAMP Involves Putative ERK Phosphorylation Sites in the C Termini of the Channel's beta- and {gamma}-Subunit
J. Biol. Chem., April 14, 2006; 281(15): 9859 - 9868.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. S. Edinger, J. Yospin, C. Perry, T. R. Kleyman, and J. P. Johnson
Regulation of Epithelial Na+ Channels (ENaC) by Methylation: A NOVEL METHYLTRANSFERASE STIMULATES ENaC ACTIVITY
J. Biol. Chem., April 7, 2006; 281(14): 9110 - 9117.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
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]

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 J. Biol. Chem.Home page
H.-L. Ji, X.-F. Su, S. Kedar, J. Li, P. Barbry, P. R. Smith, S. Matalon, and D. J. Benos
{delta}-Subunit Confers Novel Biophysical Features to {alpha}beta{gamma}-Human Epithelial Sodium Channel (ENaC) via a Physical Interaction
J. Biol. Chem., March 24, 2006; 281(12): 8233 - 8241.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
M. Yamamuro, M. Yoshimura, M. Nakayama, K. Abe, M. Shono, S. Suzuki, T. Sakamoto, Y. Saito, K. Nakao, H. Yasue, et al.
Direct Effects of Aldosterone on Cardiomyocytes in the Presence of Normal and Elevated Extracellular Sodium
Endocrinology, March 1, 2006; 147(3): 1314 - 1321.
[Abstract] [Full Text] [PDF]

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 J. Am. Soc. Nephrol.Home page
B. Pelucchi, G. Aguiari, A. Pignatelli, E. Manzati, R. Witzgall, L. del Senno, and O. Belluzzi
Nonspecific Cation Current Associated with Native Polycystin-2 in HEK-293 Cells
J. Am. Soc. Nephrol., February 1, 2006; 17(2): 388 - 397.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
H. A. Drummond, M. M. Furtado, S. Myers, S. Grifoni, K. A. Parker, A. Hoover, and D. E. Stec
ENaC proteins are required for NGF-induced neurite growth
Am J Physiol Cell Physiol, February 1, 2006; 290(2): C404 - C410.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. C. Royal, L. Bianchi, M. A. Royal, M. Lizzio Jr., G. Mukherjee, Y. O. Nunez, and M. Driscoll
Temperature-sensitive Mutant of the Caenorhabditis elegans Neurotoxic MEC-4(d) DEG/ENaC Channel Identifies a Site Required for Trafficking or Surface Maintenance
J. Biol. Chem., December 23, 2005; 280(51): 41976 - 41986.
[Abstract] [Full Text] [PDF]

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 EndocrinologyHome page
P. M. Snyder
Minireview: Regulation of Epithelial Na+ Channel Trafficking
Endocrinology, December 1, 2005; 146(12): 5079 - 5085.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. S. Amin, H.-W. Wang, E. Reza, S. C. Whitman, B. S. Tuana, and F. H. H. Leenen
Distribution of epithelial sodium channels and mineralocorticoid receptors in cardiovascular regulatory centers in rat brain
Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1787 - R1797.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A. Staruschenko, O. Pochynyuk, and J. D. Stockand
Regulation of Epithelial Na+ Channel Activity by Conserved Serine/Threonine Switches within Sorting Signals
J. Biol. Chem., November 25, 2005; 280(47): 39161 - 39167.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
O. Pochynyuk, A. Staruschenko, Q. Tong, J. Medina, and J. D. Stockand
Identification of a Functional Phosphatidylinositol 3,4,5-Trisphosphate Binding Site in the Epithelial Na+ Channel
J. Biol. Chem., November 11, 2005; 280(45): 37565 - 37571.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
M. B. Butterworth, R. A. Frizzell, J. P. Johnson, K. W. Peters, and R. S. Edinger
PKA-dependent ENaC trafficking requires the SNARE-binding protein complexin
Am J Physiol Renal Physiol, November 1, 2005; 289(5): F969 - F977.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
N. L. Jernigan and H. A. Drummond
Vascular ENaC proteins are required for renal myogenic constriction
Am J Physiol Renal Physiol, October 1, 2005; 289(4): F891 - F901.
[Abstract] [Full Text] [PDF]

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 JGPHome page
A. Adebamiro, Y. Cheng, J. P. Johnson, and R. J. Bridges
Endogenous Protease Activation of ENaC: Effect of Serine Protease Inhibition on ENaC Single Channel Properties
J. Gen. Physiol., September 26, 2005; 126(4): 339 - 352.
[Abstract] [Full Text] [PDF]

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 Behav Cogn Neurosci RevHome page
A. C. Spector and S. P. Travers
The representation of taste quality in the Mammalian nervous system.
Behav Cogn Neurosci Rev, September 1, 2005; 4(3): 143 - 191.
[Abstract] [PDF]

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 J. Am. Soc. Nephrol.Home page
S. S. Wildman, J. Marks, L. J. Churchill, C. M. Peppiatt, A. Chraibi, D. G. Shirley, J.-D. Horisberger, B. F. King, and R. J. Unwin
Regulatory Interdependence of Cloned Epithelial Na+ Channels and P2X Receptors
J. Am. Soc. Nephrol., September 1, 2005; 16(9): 2586 - 2597.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. Uc, R. F. Husted, R. L. Giriyappa, B. E. Britigan, and J. B. Stokes
Hemin induces active chloride secretion in Caco-2 cells
Am J Physiol Gastrointest Liver Physiol, August 1, 2005; 289(2): G202 - G208.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
O. A. Itani, J. B. Stokes, and C. P. Thomas
Nedd4-2 isoforms differentially associate with ENaC and regulate its activity
Am J Physiol Renal Physiol, August 1, 2005; 289(2): F334 - F346.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
O. B. Kashlan, S. Sheng, and T. R. Kleyman
On the Interaction between Amiloride and Its Putative {alpha}-Subunit Epithelial Na+ Channel Binding Site
J. Biol. Chem., July 15, 2005; 280(28): 26206 - 26215.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
C. Planes, C. Leyvraz, T. Uchida, M. A. Angelova, G. Vuagniaux, E. Hummler, M. Matthay, C. Clerici, and B. Rossier
In vitro and in vivo regulation of transepithelial lung alveolar sodium transport by serine proteases
Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1099 - L1109.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. D. Carattino, R. S. Edinger, H. J. Grieser, R. Wise, D. Neumann, U. Schlattner, J. P. Johnson, T. R. Kleyman, and K. R. Hallows
Epithelial Sodium Channel Inhibition by AMP-activated Protein Kinase in Oocytes and Polarized Renal Epithelial Cells
J. Biol. Chem., May 6, 2005; 280(18): 17608 - 17616.
[Abstract] [Full Text] [PDF]


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