Analysis of sodium self-inhibition of the epithelial sodium channel (ENaC) using classical and medium-throughput automated two-electrode voltage-clamp recordings.
Overview
- Institute for Functional Gene Analytics, Bonn-Rhein-Sieg University of Applied Sciences,Von-Liebig-Str. 20, Rheinbach, 53359 Germany
- Institute for Animal Physiology, Justus-Liebig-University,Giessen, Germany
Abstract
The epithelial sodium channel (ENaC) is a key regulator of electrolyte homeostasis and blood pressure. A characteristic ENaC feature is sodium self-inhibition (SSI), a rapid autoregulatory mechanism in which extracellular Na+ ions allosterically bind ENaC and facilitate transition into a low open probability state. Although SSI is an important functional parameter for assessing ENaC activity and gating, its quantification has traditionally relied on manual two-electrode voltage-clamp (TEVC) recordings with limited scalability and throughput. Here, we improved and evaluated experimental strategies and analytical methods for robust quantification of ENaC SSI in manual and automated TEVC systems: (1) The determination of SSI from extrapolation of transient current recordings in response to a jump in the extracellular Na+ concentration; (2) the estimation of SSI by comparison of steady-state currents before and after chemical modification of a βS520C-ENaC mutant with MTSET; and (3) quantification of SSI from the analysis of steady-state current-voltage relationships recorded at different extracellular Na+ concentrations. The latter procedure is the most reliable for SSI quantification in perfusion rate-limited automated TEVC systems. These methods can expand the capabilities of automated electrophysiology and support medium- to high-throughput investigation of autoregulatory mechanisms in ENaC variants and the discovery of novel ENaC modulators.
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Data
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- zenodo:21626248, 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/
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 6 keywords, 7 MeSH terms, 1 funder, 61 references.
Cite
This paper
Luján López, K. L., Furtwängler, N., Frank, C. M., Althaus, M., & Rauh, O. (2026). Analysis of sodium self-inhibition of the epithelial sodium channel (ENaC) using classical and medium-throughput automated two-electrode voltage-clamp recordings. Pflugers Archiv : European journal of physiology, 478(10), 82. https://
BibTeX
@article{lujanlopez2026a
author = {Luján López, Karen Lizet and Furtwängler, Nadja and Frank, Carol Merlin and Althaus, Mike and Rauh, Oliver},
title = {{Analysis of sodium self-inhibition of the epithelial sodium channel (ENaC) using classical and medium-throughput automated two-electrode voltage-clamp recordings}},
journal = {Pflugers Archiv : European journal of physiology},
year = {2026},
month = sep,
volume = {478},
number = {10},
pages = {82},
publisher = {Springer Science+Business Media},
issn = {0031-6768},
doi = {10.1007/
url = {https://
pmid = {42802231},
pmcid = {PMC13616839}
}
RIS
TY - JOUR
AU - Luján López, Karen Lizet
AU - Furtwängler, Nadja
AU - Frank, Carol Merlin
AU - Althaus, Mike
AU - Rauh, Oliver
TI - Analysis of sodium self-inhibition of the epithelial sodium channel (ENaC) using classical and medium-throughput automated two-electrode voltage-clamp recordings
T2 - Pflugers Archiv : European journal of physiology
J2 - Pflugers Arch
PY - 2026
DA - 2026/
VL - 478
IS - 10
SP - 82
SN - 0031-6768
PB - Springer Science+Business Media
DO - 10.1007/
UR - https://
LA - en
ER -
CSL-JSON
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"volume": "478",
"issue": "10",
"page": "82",
"DOI": "10.1007/
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"URL": "https://
"language": "en",
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