96 K. Mruk and W. R. Kobertz
dent channel ligand, an acrylamide electrophile, and the photocleavable chromo-
phore, nitroindoline. Using live cell imaging, the authors showed they could label
exogenously expressed channels in HEK293 cells or native neurons from dissoci-
ated hippocampal cultures. This study demonstrates the utility of delivering small
probes to an ion channel subunit without perturbing channel function.
Bioreactive tethers have been widely successful in gathering structural informa-
tion about ion channels and now provide an approach to selectively label endoge-
nous subunits in native cells. To date, these approaches have been limited to probing
the extracellular surface of ion channel complexes. Membrane permeant bioreactive
tethers with bioorthogonal functional groups would provide access to the cytoplas-
mic regions of ion channels, enabling the investigation of water-soluble regulatory
subunits and cofactors. This migration to innovative chemistries will provide a new
arsenal of bioreactive tethers to poke, prod, and manipulate ion channel complexes
in cells and living organisms.
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