Sunday, 20 July, 2014
Controlling epithelial sodium channels with light using photoswitchable amilorides
M. Schönberger, M. Althaus, M. Fronius, W. Clauss, and D. Trauner -
Nature Chem., doi:10.1038/nchem.2004, published online: 20 July 2014
Amiloride is a widely used diuretic that blocks epithelial sodium channels (ENaCs). These heterotrimeric transmembrane proteins, assembled from , and or subunits, effectively control water transport across epithelia and sodium influx into non-epithelial cells. The functional role of ENaC in various organs, including the human brain, is still poorly understood and no pharmacological tools are available for the functional differentiation between - and -containing ENaCs. Here we report several photoswitchable versions of amiloride. One compound, termed PA1, enables the optical control of ENaC channels, in particular the isoform, by switching between blue and green light, or by turning on and off blue light. PA1 was used to modify functionally ENaC in amphibian and mammalian cells. We also show that PA1 can be used to differentiate between ENaC and ENaC in a model for the human lung epithelium.