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A novel family of small molecule inhibitors of voltage-gated sodium channels (NaVs) based on the structure of batrachotoxin (BTX), a well-known channel agonist, is described. Protein mutagenesis and electrophysiology experiments reveal the binding site as the inner pore region of the channel, analogous to BTX, alkaloid toxins, and local anesthetics. Homology modeling of the eukaryotic channel based on recent crystallographic analyses of bacterial NaVs suggests a mechanism of action for ion conduction block.


Tatsuya Toma, Matthew M Logan, Frederic Menard, A Sloan Devlin, J Du Bois. Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin. ACS chemical neuroscience. 2016 Aug 8

PMID: 27501251

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