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Gd 3+ and Gd 3+ ‐containing contrast agents affect human ENaC activity in Xenopus ocytes (1181.14)
Author(s) -
Knoepp Fenja,
Clauss Wolfgang,
Fronius Martin
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1181.14
Subject(s) - epithelial sodium channel , xenopus , chemistry , gadolinium , sodium channel , gating , sodium , biophysics , biochemistry , biology , organic chemistry , gene
In lungs, activity of epithelial sodium‐channel (ENaC) is crucial for regulating the volume and composition of epithelial lining fluid, since dysfunction of this process is associated with diseases, e.g. pulmonary oedema. This study examined a potential impact of Gd 3+ , a core‐part of nebulized contrast‐agents used for magnetic‐resonance‐imaging ( MRI ) of lungs, on activity of human ENaC (hENAC). hENaC was expressed in Xenopus laevis oocytes and membrane currents (I M ) were recorded by Two‐Electrode‐Voltage‐Clamp measurements.Gd 3+ dose‐dependently affected hENaC activity. 0.1mM decreased (17±1 %), whereas 0.5mM induced an increase of I M (27±4 %). Activation by 0.5mM Gd 3+ was due to an interference with self‐inhibition (SI) of hENaC (control: 40±3 %; Gd 3+ : 25±4 %) whereas 0.1mM did not affect SI (control: 32±8 %; Gd 3+ : 33±7 %). Interestingly, the cysteine modifying compound MTSEA prevented ENaC activation by 0.5mM Gd 3+ (the effect by 0.1mM was not affected), whereas histidine‐modifying DEPC prevented inhibition by 0.1mM Gd 3+ and did not affect the Gd 3+ induced activation. Gd‐DTPA, a Gd 3+ ‐containing contrast agent, showed comparable effects to 0.1mM. These results argue for multiple Gd 3+ ‐binding sites that differentially affect ENaC activity and demonstrate that Gd 3+ containing contrast agents can directly interfere with ENaC activity. Grant Funding Source : FK is supported by a scholarship from the university of Giessen