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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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