Gd3+ and Gd3+‐containing contrast agents affect human ENaC activity in Xenopus ocytes (1181.14)

Abstract

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 Gd3+, 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 (IM) were recorded by Two‐Electrode‐Voltage‐Clamp measurements.Gd3+ dose‐dependently affected hENaC activity. 0.1mM decreased (17±1 %), whereas 0.5mM induced an increase of IM (27±4 %). Activation by 0.5mM Gd3+ was due to an interference with self‐inhibition (SI) of hENaC (control: 40±3 %; Gd3+: 25±4 %) whereas 0.1mM did not affect SI (control: 32±8 %; Gd3+: 33±7 %). Interestingly, the cysteine modifying compound MTSEA prevented ENaC activation by 0.5mM Gd3+ (the effect by 0.1mM was not affected), whereas histidine‐modifying DEPC prevented inhibition by 0.1mM Gd3+ and did not affect the Gd3+ induced activation. Gd‐DTPA, a Gd3+‐containing contrast agent, showed comparable effects to 0.1mM. These results argue for multiple Gd3+‐binding sites that differentially affect ENaC activity and demonstrate that Gd3+ containing contrast agents can directly interfere with ENaC activity.Grant Funding Source: FK is supported by a scholarship from the university of Giessen