2. Academic Validation
  3. Controlling epithelial sodium channels with light using photoswitchable amilorides

Controlling epithelial sodium channels with light using photoswitchable amilorides

  • Nat Chem. 2014 Aug;6(8):712-9. doi: 10.1038/nchem.2004.
Matthias Schönberger 1,  Mike Althaus 2,  Martin Fronius 3,  Wolfgang Clauss 2,  Dirk Trauner 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians-Universität München, Butenandtstraße 5-13 (F4.086), 81377 Munich, Germany.
  • 2 Institute of Animal Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26, 35392 Giessen, Germany.
  • 3 1] Institute of Animal Physiology, Justus Liebig University Giessen, Heinrich-Buff-Ring 26, 35392 Giessen, Germany [2] Department of Physiology, University of Otago, PO Box 913, Dunedin 9054, New Zealand.
PMID: 25054942 DOI: 10.1038/nchem.2004
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.

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