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Coupled movement of a sodium ion and ligand QX-222 in the closed cardiac sodium channel (1)

In the schematic, the permanently charged QX-222 reaches the inner pore via III/IV repeat interface and displaces the resident ion that leaves the central cavity through the selectivity filter. QX-222, a lidocaine derivative, is a sodium channel blocker. (Source: Tikhonov DB, Zhorov BS. Predicting structural details of the sodium channel pore basing on animal toxin studies. Front Pharmacol 2018;9:880. See also: Bruhova I, Tikhonov DB, Zhorov BS. Access and binding of local anesthetics in the closed sodium channel. Mol Pharmacol 2008;74[4]:1033-45. Creative Commons Attribution [CC BY] license.)