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Positive Allosteric Modulation Of Kv Channels By Sevoflurane: Insights Into The Structural Basis Of Inhaled Anesthetic Action., Qiansheng Liang, Warren D Anderson, Shelly T Jones, Caio S Souza, Juliana M Hosoume, Werner Treptow, Manuel Covarrubias

Department of Neuroscience Faculty Papers

Inhalational general anesthesia results from the poorly understood interactions of haloethers with multiple protein targets, which prominently includes ion channels in the nervous system. Previously, we reported that the commonly used inhaled anesthetic sevoflurane potentiates the activity of voltage-gated K+ (Kv) channels, specifically, several mammalian Kv1 channels and the Drosophila K-Shaw2 channel. Also, previous work suggested that the S4-S5 linker of K-Shaw2 plays a role in the inhibition of this Kv channel by n-alcohols and inhaled anesthetics. Here, we hypothesized that the S4-S5 linker is also a determinant of the potentiation of Kv1.2 and K-Shaw2 by sevoflurane. Following functional expression …