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Controlling epithelial sodium channels with light using photoswitchable amilorides

Lookup NU author(s): Dr Mike Althaus

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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.

Publication metadata

Author(s): Schönberger M, Althaus M, Fronius M, Clauss W, Trauner D

Publication type: Article

Publication status: Published

Journal: Nature Chemistry

Year: 2014

Volume: 6

Pages: 712-719

Print publication date: 31/08/2014

Online publication date: 20/07/2014

Acceptance date: 12/06/2014

ISSN (print): 1755-4330

ISSN (electronic): 1755-4349

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/nchem.2004

DOI: 10.1038/nchem.2004

PubMed id: 25054942

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