TY - JOUR
T1 - Controlling epithelial sodium channels with light using photoswitchable amilorides
AU - Schönberger, Matthias
AU - Althaus, Mike
AU - Fronius, Martin
AU - Clauss, Wolfgang
AU - Trauner, Dirk
N1 - Funding Information:
We thank the European Research Commission for an ERC Advanced Grant (Grant No. 268795 to D.T.). M.A. is supported by grants from the German Research Foundation (AL1453/1-1 and AL1453/1-2), M.F. and W.C. acknowledge a grant provided by the Federal State of Hesse (LOEWE Research Focus, Non-neuronal cholinergic systems). M.S. was supported by a grant from the German Study Foundation and the International Max Planck Research School (IMPRS-LS). We acknowledge the support of K. Hüll (chemical synthesis) and L. de la Osa de la Rosa (cell-culture work), and we thank D. Barber for helpful comments. We also thank D. Alvarez de la Rosa for providing constructs of all ENaC subunits in pcDNA3.1.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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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U2 - 10.1038/nchem.2004
DO - 10.1038/nchem.2004
M3 - Article
C2 - 25054942
AN - SCOPUS:84904801796
SN - 1755-4330
VL - 6
SP - 712
EP - 719
JO - Nature Chemistry
JF - Nature Chemistry
IS - 8
ER -