An External Site Controls Closing of the Epithelial Na+ Channel ENaC
Open Access
- 1 September 2002
- journal article
- Published by Wiley in The Journal of Physiology
- Vol. 543 (2), 413-424
- https://doi.org/10.1113/jphysiol.2002.022020
Abstract
Members of the ENaC/degenerin family of ion channels include the epithelial sodium channel (ENaC), acid‐sensing ion channels (ASICs) and the nematode Caenorhabditis elegans degenerins. These channels are activated by a variety of stimuli such as ligands (ASICs) and mechanical forces (degenerins), or otherwise are constitutively active (ENaC). Despite their functional heterogeneity, these channels might share common basic mechanisms for gating. Mutations of a conserved residue in the extracellular loop, namely the ‘degenerin site’ activate all members of the ENaC/degenerin family. Chemical modification of a cysteine introduced in the degenerin site of rat ENaC (βS518C) by the sulfhydryl reagents MTSET or MTSEA, results in a ∼3‐fold increase in the open probability. This effect is due to an 8‐fold shortening of channel closed times and an increase in the number of long openings. In contrast to the intracellular gating domain in the N‐terminus which is critical for channel opening, the intact extracellular degenerin site is necessary for normal channel closing, as illustrated by our observation that modification of βS518C destabilises the channel closed state. The modification by the sulfhydryl reagents is state‐ and size‐dependent consistent with a conformational change of the degenerin site during channel opening and closing. We propose that the intracellular and extracellular modulatory sites act on a common channel gate and control the activity of ENaC at the cell surface.Keywords
This publication has 35 references indexed in Scilit:
- Epithelial Sodium Channel Pore RegionPublished by Elsevier ,2001
- The Croonian Lecture 2000. Nicotinic acetylcholine receptor and the structural basis of fast synaptic transmission,Lecture delivered 5 October 2000 at University College LondonPhilosophical Transactions Of The Royal Society B-Biological Sciences, 2000
- Gating Induces a Conformational Change in the Outer Vestibule of EnacThe Journal of general physiology, 2000
- Characterization of the Selectivity Filter of the Epithelial Sodium ChannelPublished by Elsevier ,2000
- Regulation of Na+channels by luminal Na+in rat cortical collecting tubuleThe Journal of Physiology, 1998
- MOLECULAR MODELING OF MECHANOTRANSDUCTION IN THE NEMATODE CAENORHABDITIS ELEGANSAnnual Review of Physiology, 1997
- Identification of Amino Acid Residues in the α, β, and γ Subunits of the Epithelial Sodium Channel (ENaC) Involved in Amiloride Block and Ion PermeationThe Journal of general physiology, 1997
- Dynamic Rearrangement of the Outer Mouth of a K+ Channel during GatingNeuron, 1996
- Gating of Na channels in the rat cortical collecting tubule: effects of voltage and membrane stretch.The Journal of general physiology, 1996
- The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degenerationNature, 1991