Guinea pig δβγ-ENaC is locked in an open state and uncoupled from regulation by proteases.

Overview

Authors: Rene Yufenyuy Lawong^1,2, Etang Collins Etang¹, Fabian May¹, Philipp Vorrat¹, Oliver Rauh¹, Mike Althaus¹

ORCID iDs: Rene Yufenyuy Lawong, Etang Collins Etang, Fabian May, Philipp Vorrat, Oliver Rauh, Mike Althaus

Institute for Functional Gene Analytics, Bonn-Rhein-Sieg University of Applied Sciences, Von-Liebig-Str. 20, 53359 Rheinbach, Germany
Institute for Animal Physiology, Justus-Liebig-University, Giessen, Germany

Institutions: Hochschule Bonn-Rhein-Sieg (Germany); Justus-Liebig-Universität Gießen (Germany)

Journal: Pflugers Archiv : European journal of physiology, volume 478, issue 5, article 43

Dates: received 5 January 2026; accepted 14 April 2026; published online 25 April 2026; in print 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1007/s00424-026-03173-0 · PMID 42032333 · PMCID PMC13109204 · OpenAlex W7155535766

Open access: hybrid, a free copy (OpenAlex)

Status: data only

Categories: intracellular / patch clamp (modality), other (organism), cellular / molecular (subfield)

Methods: Connectivity

Keywords: Epithelial Sodium Channel, ENaC, SCNN1D, Protease

MeSH: Epithelial Sodium Channels*, Ion Channel Gating*, Peptide Hydrolases*, Animals, Chymotrypsin, Female, Furin, Guinea Pigs, Oocytes, Protein Subunits, Trypsin, Xenopus laevis (* major topic)

Topic: Complement system in diseases (Immunology, Immunology and Microbiology), according to OpenAlex

Funding: Hochschule Bonn-Rhein-Sieg University of Applied Sciences; Deutsche Forschungsgemeinschaft

Citations: cited by 1 paper (Europe PMC); 38 references in the paper

Abstract

The epithelial sodium channel (ENaC) plays a key role in salt and water homeostasis in tetrapod vertebrates. There are four ENaC subunits (α, β, γ and δ) which form heterotrimeric αβγ- or δβγ-ENaC assemblies. ENaC activity is tightly coupled to proteolytic processing of ENaC subunits, but this effect is specific to ENaC subunit assembly and mechanistically not completely understood. Guinea pig αβγ- or δβγ-ENaCs were heterologously expressed in Xenopus oocytes and their control by extracellular proteases was investigated using protein biochemistry, two-electrode voltage-clamp and patch-clamp electrophysiology. Guinea pig αβγ-ENaC activity was tightly coupled to cleavage of its α- and γ-subunits by the endoprotease furin and extracellular chymotrypsin or trypsin. By contrast, δβγ-ENaC activity was not affected by proteases, despite cleavage of its γ-subunit by chymotrypsin. Experiments using a βS521C-ENaC substitution, which locks ENaC in an open state after exposure to the sulfhydryl-reagent [2-(trimethylammonium)ethyl] methanethiosulfonate (MTSET), demonstrated that guinea pig δβS521Cγ-ENaCs are almost fully open when expressed in Xenopus oocytes. On-cell single-channel patch-clamp recordings confirmed that the open probability of guinea pig δβγ-ENaC is nearly 90%. These data indicate that guinea pig δβγ-ENaC is locked in an open state and thereby uncoupled from channel control by proteases.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00424-026-03173-0.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

zenodo:18145489, at Zenodo; found in “Data availability”

Data availability

Data are made available in the manuscript, and as Source Data deposited at the Zenodo data depository (10.5281/zenodo.18145489).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 4 keywords, 12 MeSH terms, 2 funders, 38 references.

Cite

This paper

Lawong, R. Y., Etang, E. C., May, F., Vorrat, P., Rauh, O., & Althaus, M. (2026). Guinea pig δβγ-ENaC is locked in an open state and uncoupled from regulation by proteases. Pflugers Archiv : European journal of physiology, 478(5), 43. https://doi.org/10.1007/s00424-026-03173-0

BibTeX

@article{lawong2026guinea, author = {Lawong, Rene Yufenyuy and Etang, Etang Collins and May, Fabian and Vorrat, Philipp and Rauh, Oliver and Althaus, Mike}, title = {{Guinea pig δβγ-ENaC is locked in an open state and uncoupled from regulation by proteases}}, journal = {Pflugers Archiv : European journal of physiology}, year = {2026}, month = apr, volume = {478}, number = {5}, pages = {43}, publisher = {Springer Science+Business Media}, issn = {0031-6768}, doi = {10.1007/s00424-026-03173-0}, url = {https://doi.org/10.1007/s00424-026-03173-0}, pmid = {42032333}, pmcid = {PMC13109204} }

RIS

TY - JOUR AU - Lawong, Rene Yufenyuy AU - Etang, Etang Collins AU - May, Fabian AU - Vorrat, Philipp AU - Rauh, Oliver AU - Althaus, Mike TI - Guinea pig δβγ-ENaC is locked in an open state and uncoupled from regulation by proteases T2 - Pflugers Archiv : European journal of physiology J2 - Pflugers Arch PY - 2026 DA - 2026/04/25 VL - 478 IS - 5 SP - 43 SN - 0031-6768 PB - Springer Science+Business Media DO - 10.1007/s00424-026-03173-0 UR - https://doi.org/10.1007/s00424-026-03173-0 LA - en ER -

CSL-JSON

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