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• W2324150973 endingPage "1047" @default.
• W2324150973 startingPage "1038" @default.
• W2324150973 abstract "In Brief BACKGROUND: Inward rectifier K+ channels of the Kir2.x subfamily are widely expressed in neuronal tissues, controlling neuronal excitability. Previous studies reported that local anesthetics (LAs) do not affect Kir2 channels. However, the effects have not been studied at large concentrations used in regional anesthesia. METHODS: This study used the patch-clamp technique to examine the effects of bupivacaine and lidocaine on Kir2.1, Kir2.2, and Kir2.3 channels expressed in human embryonic kidney 293 cells. RESULTS: When applied extracellularly in whole-cell recordings, both LAs inhibited Kir2.x currents in a voltage-independent manner. Inhibition with bupivacaine was slow and irreversible, whereas that with lidocaine was fast and reversible. Kir2.3 displayed a greater sensitivity to bupivacaine than Kir2.1 and Kir2.2 (50% inhibitory concentrations at approximately 5 minutes, 0.6 vs 8–10 mM), whereas their sensitivities to lidocaine were similar (50% inhibitory concentrations, 1.5–2.7 mM). Increases in the charged/neutral ratio of the LAs at an acidic extracellular pH attenuated their inhibitory effects, and a permanently charged lidocaine derivative QX-314 exhibited no effects when applied extracellularly. Inside-out experiments demonstrated that inhibition of Kir2.1 with cytoplasmic lidocaine and QX-314 was rapid and reversible, whereas that induced by bupivacaine was slow and irreversible. Furthermore, dose-inhibition relations for the charged form of bupivacaine and lidocaine obtained at different cytoplasmic pHs could be approximated by a single relation for each LA. CONCLUSIONS: The results indicate that both LAs at clinical concentrations equilibrated rapidly with the intracellular milieu, differentially inhibiting Kir2.x channel function from the cytoplasmic side. Published ahead of print January 11, 2016" @default.
• W2324150973 created "2016-06-24" @default.
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• W2324150973 date "2016-04-01" @default.
• W2324150973 modified "2023-09-27" @default.
• W2324150973 title "Clinical Concentrations of Local Anesthetics Bupivacaine and Lidocaine Differentially Inhibit Human Kir2.x Inward Rectifier K+ Channels" @default.
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• W2324150973 doi "https://doi.org/10.1213/ane.0000000000001137" @default.
• W2324150973 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26756912" @default.
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