Faculty Collaboration Database

Insight toward epithelial Na+ channel mechanism revealed by the acid-sensing ion channel 1 structure. IUBMB Life 2008 Sep;60(9):620-8

Date

05/07/2008

Pubmed ID

18459164

DOI

10.1002/iub.89

Scopus ID

2-s2.0-56149115546 (requires institutional sign-in at Scopus site)   91 Citations

Abstract

The epithelial Na(+) channel/degenerin (ENaC/DEG) protein family includes a diverse group of ion channels, including nonvoltage-gated Na(+) channels of epithelia and neurons, and the acid-sensing ion channel 1 (ASIC1). In mammalian epithelia, ENaC helps regulate Na(+) and associated water transport, making it a critical determinant of systemic blood pressure and pulmonary mucosal fluidity. In the nervous system, ENaC/DEG proteins are related to sensory transduction. While the importance and physiological function of these ion channels are established, less is known about their structure. One hallmark of the ENaC/DEG channel family is that each channel subunit has only two transmembrane domains connected by an exceedingly large extracellular loop. This subunit structure was recently confirmed when Jasti and colleagues determined the crystal structure of chicken ASIC1, a neuronal acid-sensing ENaC/DEG channel. By mapping ENaC to the structural coordinates of cASIC1, as we do here, we hope to provide insight toward ENaC structure. ENaC, like ASIC1, appears to be a trimeric channel containing 1alpha, 1beta, and 1gamma subunit. Heterotrimeric ENaC and monomeric ENaC subunits within the trimer possibly contain many of the major secondary, tertiary, and quaternary features identified in cASIC1 with a few subtle but critical differences. These differences are expected to have profound effects on channel behavior. In particular, they may contribute to ENaC insensitivity to acid and to its constitutive activity in the absence of time- and ligand-dependent inactivation. Experiments resulting from this comparison of cASIC1 and ENaC may help clarify unresolved issues related to ENaC architecture, and may help identify secondary structures and residues critical to ENaC function.

Author List

Stockand JD, Staruschenko A, Pochynyuk O, Booth RE, Silverthorn DU

MESH terms used to index this publication - Major topics in bold

Acid Sensing Ion Channels
Amino Acid Sequence
Animals
Epithelial Sodium Channels
Humans
Ion Channel Gating
Models, Molecular
Molecular Sequence Data
Nerve Tissue Proteins
Protein Structure, Quaternary
Protein Structure, Tertiary
Protein Subunits
Sequence Alignment
Sodium
Sodium Channels