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Physiological Reviews, Vol. 82, No. 3, July 2002, pp. 735-767; 10.1152/physrev.00007.2002.
Copyright ©2002 by the American Physiological Society
Institut de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland
Kellenberger, Stephan and
Laurent Schild.
Epithelial Sodium Channel/Degenerin Family of Ion Channels: A
Variety of Functions for a Shared Structure. Physiol. Rev. 82: 735-767, 2002.
The recently discovered
epithelial sodium channel (ENaC)/degenerin (DEG) gene family encodes
sodium channels involved in various cell functions in metazoans.
Subfamilies found in invertebrates or mammals are functionally
distinct. The degenerins in Caenorhabditis elegans
participate in mechanotransduction in neuronal cells, FaNaC in snails
is a ligand-gated channel activated by neuropeptides, and the
Drosophila subfamily is expressed in gonads and neurons. In
mammals, ENaC mediates Na+ transport in epithelia and is
essential for sodium homeostasis. The ASIC genes encode
proton-gated cation channels in both the central and peripheral
nervous system that could be involved in pain transduction. This review
summarizes the physiological roles of the different channels belonging
to this family, their biophysical and pharmacological characteristics,
and the emerging knowledge of their molecular structure. Although
functionally different, the ENaC/DEG family members share functional
domains that are involved in the control of channel activity and in the
formation of the pore. The functional heterogeneity among the members
of the ENaC/DEG channel family provides a unique opportunity to address the molecular basis of basic channel functions such as activation by
ligands, mechanotransduction, ionic selectivity, or block by pharmacological ligands.
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F. Mercado, I. A. Lopez, D. Acuna, R. Vega, and E. Soto Acid-Sensing Ionic Channels in the Rat Vestibular Endorgans and Ganglia J Neurophysiol, September 1, 2006; 96(3): 1615 - 1624. [Abstract] [Full Text] [PDF]
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J. Yagi, H. N. Wenk, L. A. Naves, and E. W. McCleskey Sustained Currents Through ASIC3 Ion Channels at the Modest pH Changes That Occur During Myocardial Ischemia Circ. Res., September 1, 2006; 99(5): 501 - 509. [Abstract] [Full Text] [PDF]
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V. I. Pidoplichko and J. A. Dani Acid-sensitive ionic channels in midbrain dopamine neurons are sensitive to ammonium, which may contribute to hyperammonemia damage PNAS, July 25, 2006; 103(30): 11376 - 11380. [Abstract] [Full Text] [PDF]
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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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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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D. Loffing-Cueni, S. Y. Flores, D. Sauter, D. Daidie, N. Siegrist, P. Meneton, O. Staub, and J. Loffing Dietary Sodium Intake Regulates the Ubiquitin-Protein Ligase Nedd4-2 in the Renal Collecting System J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1264 - 1274. [Abstract] [Full Text] [PDF]
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Y. Pfister, I. Gautschi, A.-N. Takeda, M. van Bemmelen, S. Kellenberger, and L. Schild A Gating Mutation in the Internal Pore of ASIC1a J. Biol. Chem., April 28, 2006; 281(17): 11787 - 11791. [Abstract] [Full Text] [PDF]
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D. Olteanu, B. K. Yoder, W. Liu, M. J. Croyle, E. A. Welty, K. Rosborough, J. M. Wyss, P. D. Bell, L. M. Guay-Woodford, M. O. Bevensee, et al. Heightened epithelial Na+ channel-mediated Na+ absorption in a murine polycystic kidney disease model epithelium lacking apical monocilia Am J Physiol Cell Physiol, April 1, 2006; 290(4): C952 - C963. [Abstract] [Full Text] [PDF]
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Q. Tong, A. G. Menon, and J. D. Stockand Functional polymorphisms in the {alpha}-subunit of the human epithelial Na+ channel increase activity Am J Physiol Renal Physiol, April 1, 2006; 290(4): F821 - F827. [Abstract] [Full Text] [PDF]
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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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E. O. Hernandez-Gonzalez, J. Sosnik, J. Edwards, J. J. Acevedo, I. Mendoza-Lujambio, I. Lopez-Gonzalez, I. Demarco, E. Wertheimer, A. Darszon, and P. E. Visconti Sodium and Epithelial Sodium Channels Participate in the Regulation of the Capacitation-associated Hyperpolarization in Mouse Sperm J. Biol. Chem., March 3, 2006; 281(9): 5623 - 5633. [Abstract] [Full Text] [PDF]
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Z. Gao, O. Henig, V. Kehoe, L. I. Sinoway, and J. Li Vanilloid type 1 receptor and the acid-sensing ion channel mediate acid phosphate activation of muscle afferent nerves in rats J Appl Physiol, February 1, 2006; 100(2): 421 - 426. [Abstract] [Full Text] [PDF]
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W. Yan, L. Suaud, T. R. Kleyman, and R. C. Rubenstein Differential modulation of a polymorphism in the COOH terminus of the {alpha}-subunit of the human epithelial sodium channel by protein kinase C{delta} Am J Physiol Renal Physiol, February 1, 2006; 290(2): F279 - F288. [Abstract] [Full Text] [PDF]
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M. Salinas, L. D. Rash, A. Baron, G. Lambeau, P. Escoubas, and M. Lazdunski The receptor site of the spider toxin PcTx1 on the proton-gated cation channel ASIC1a J. Physiol., January 15, 2006; 570(2): 339 - 354. [Abstract] [Full Text] [PDF]
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M. Vukicevic, G. Weder, A. Boillat, A. Boesch, and S. Kellenberger Trypsin Cleaves Acid-sensing Ion Channel 1a in a Domain That Is Critical for Channel Gating J. Biol. Chem., January 13, 2006; 281(2): 714 - 722. [Abstract] [Full Text] [PDF]
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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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H. Abriel and O. Staub Ubiquitylation of Ion Channels Physiology, December 1, 2005; 20(6): 398 - 407. [Abstract] [Full Text] [PDF]
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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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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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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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 H. Yamamura, S. Ugawa, T. Ueda, and S. Shimada Evans Blue Is a Specific Antagonist of the Human Epithelial Na+ Channel {delta}-Subunit J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 965 - 969. [Abstract] [Full Text] [PDF]
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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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O. Staub and F. Verrey Impact of Nedd4 Proteins and Serum and Glucocorticoid-Induced Kinases on Epithelial Na+ Transport in the Distal Nephron J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3167 - 3174. [Abstract] [Full Text] [PDF]
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J. Loffing and L. Schild Functional Domains of the Epithelial Sodium Channel J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3175 - 3181. [Full Text] [PDF]
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 J. S. Mogil, N. M. Breese, M.-F. Witty, J. Ritchie, M.-L. Rainville, A. Ase, N. Abbadi, C. L. Stucky, and P. Seguela Transgenic Expression of a Dominant-Negative ASIC3 Subunit Leads to Increased Sensitivity to Mechanical and Inflammatory Stimuli J. Neurosci., October 26, 2005; 25(43): 9893 - 9901. [Abstract] [Full Text] [PDF]
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 H. Yamamura, S. Ugawa, T. Ueda, M. Nagao, and S. Shimada Icilin Activates the {delta}-Subunit of the Human Epithelial Na+ Channel Mol. Pharmacol., October 1, 2005; 68(4): 1142 - 1147. [Abstract] [Full Text] [PDF]
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