Controlling epithelial sodium channels with light using photoswitchable amilorides

Matthias Schönberger, Mike Althaus, Martin Fronius, Wolfgang Clauss, Dirk Trauner

Research output: Contribution to journalArticle

Abstract

Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from β, γ and α or δ subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of δβγENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between α- and δ-containing ENaCs. Here we report several photoswitchable versions of amiloride. One compound, termed PA1, enables the optical control of ENaC channels, in particular the δβγ isoform, by switching between blue and green light, or by turning on and off blue light. PA1 was used to modify functionally δβγENaC in amphibian and mammalian cells. We also show that PA1 can be used to differentiate between δβγENaC and αβγENaC in a model for the human lung epithelium.

Original languageEnglish (US)
Pages (from-to)712-719
Number of pages8
JournalNature Chemistry
Volume6
Issue number8
DOIs
StatePublished - 2014

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Epithelial Sodium Channels
Amiloride
Cells
Sodium
Methyl Green
Diuretics
Brain
Protein Isoforms
Proteins
Water

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

Cite this

Schönberger, M., Althaus, M., Fronius, M., Clauss, W., & Trauner, D. (2014). Controlling epithelial sodium channels with light using photoswitchable amilorides. Nature Chemistry, 6(8), 712-719. https://doi.org/10.1038/nchem.2004

Controlling epithelial sodium channels with light using photoswitchable amilorides. / Schönberger, Matthias; Althaus, Mike; Fronius, Martin; Clauss, Wolfgang; Trauner, Dirk.

In: Nature Chemistry, Vol. 6, No. 8, 2014, p. 712-719.

Research output: Contribution to journalArticle

Schönberger, M, Althaus, M, Fronius, M, Clauss, W & Trauner, D 2014, 'Controlling epithelial sodium channels with light using photoswitchable amilorides', Nature Chemistry, vol. 6, no. 8, pp. 712-719. https://doi.org/10.1038/nchem.2004
Schönberger, Matthias ; Althaus, Mike ; Fronius, Martin ; Clauss, Wolfgang ; Trauner, Dirk. / Controlling epithelial sodium channels with light using photoswitchable amilorides. In: Nature Chemistry. 2014 ; Vol. 6, No. 8. pp. 712-719.
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