Epithelial sodium channel: a ligand-gated channel?
The epithelial sodium channel (ENaC) is a key component of the transepithelial Na+ transport. In epithelia, it is responsible for the maintenance of Na+ balance (which in turn controls extracellular fluid volume and arterial blood pressure) and the regulation of airway surface fluid. While the regulation of channel synthesis and surface density have been well described, the control of channel opening is still poorly understood. The channel has a large extracellular domain of as yet unknown function; a number of extracellular factors have been shown to modulate ENaC activity, including extracellular Na+ itself (through a phenomenon called 'self-inhibition'), several other organic or inorganic cations, which seem to interfere with self-inhibition, and serine proteases. Although a direct interaction with the extracellular domain of ENaC has not yet been demonstrated for each of these modulators, the available data strongly suggest that ENaC behaves as a ligand-gated channel similar to several other members of the ENaC/degenerin family.
Institut de Pharmacologie et de Toxicologie, Université de Lausanne, Lausanne, Switzerland. Jean-Daniel.Horisberger@ipharm.unil.ch
Jean-Daniel
JD
Horisberger
Ahmed
A
Chraïbi
D000818:Animals; D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D015222:Sodium Channels / Q000737:chemistry / Q000378:metabolism*
D062626:Degenerin Sodium Channels; D053503:Epithelial Sodium Channels; D007473:Ion Channels; D008024:Ligands; D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D012964:Sodium; D012697:Serine Endopeptidases