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- W2334300363 abstract "(1) Local anaesthetics (LA) rely for their clinical actions on state-dependent inhibition of voltage-dependent sodium channels. (2) Single, batrachoxin-modified sodium channels in planar lipid bilayers allow direct observation of drug-channel interactions. Two modes of inhibition of single-channel current are observed: fast block of the open channels and prolongation of a long-lived closed state, some of whose properties resemble those of the inactivated state of unmodified channels. (3) Analogues of different parts of the LA molecule separately mimic each blocking mode: amines—fast block, and water-soluble aromatics—closed state prolongation. (4) Interaction between a μ-conotoxin derivative and diethylammonium indicate an intrapore site of fast, open-state block. (5) Site-directed mutagenesis studies suggest that hydrophobic residues in transmembrane segment 6 of repeat domain 4 of sodium channels are critical for both LA binding and stabilization of the inactivated state." @default.
- W2334300363 created "2016-06-24" @default.
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- W2334300363 date "2011-08-01" @default.
- W2334300363 modified "2023-09-25" @default.
- W2334300363 title "Cocaine arrhythmias: From the sodium channel to the bedside" @default.
- W2334300363 doi "https://doi.org/10.1016/j.toxlet.2011.05.121" @default.
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