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    Looger LabSternson Lab
    09/02/11 | Chemical and genetic engineering of selective ion channel-ligand interactions.
    Magnus CJ, Lee PH, Atasoy D, Su HH, Looger LL, Sternson SM
    Science. 2011 Sep 2;333(6047):1292-6. doi: 10.1126/science.1206606

    Ionic flux mediates essential physiological and behavioral functions in defined cell populations. Cell type-specific activators of diverse ionic conductances are needed for probing these effects. We combined chemistry and protein engineering to enable the systematic creation of a toolbox of ligand-gated ion channels (LGICs) with orthogonal pharmacologic selectivity and divergent functional properties. The LGICs and their small-molecule effectors were able to activate a range of ionic conductances in genetically specified cell types. LGICs constructed for neuronal perturbation could be used to selectively manipulate neuron activity in mammalian brains in vivo. The diversity of ion channel tools accessible from this approach will be useful for examining the relationship between neuronal activity and animal behavior, as well as for cell biological and physiological applications requiring chemical control of ion conductance.

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