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• W2121707070 abstract "Gating of voltage-gated K(+) channels (K(v) channels) depends on the electromechanical coupling between the voltage sensor and activation gate. The main activation gate of K(v) channels involves the COOH-terminal section of the S6 segment (S6-b) and the S4-S5 linker at the intracellular mouth of the pore. In this study, we have expanded our earlier work to probe the concerted contribution of these regions to the putative amphipathic 1-alkanol site in the Shaw2 K(+) channel. In the S4-S5 linker, we found a direct energetic correlation between alpha-helical propensity and the inhibition of the Shaw2 channel by 1-butanol. Spectroscopic structural analyses of the S4-S5 linker supported this correlation. Furthermore, the analysis of chimeric Shaw2 and K(v)3.4 channels that exchanged their corresponding S4-S5 linkers showed that the potentiation induced by 1-butanol depends on the combination of a single mutation in the S6 PVPV motif (PVAV) and the presence of the Shaw2 S4-S5 linker. Then, using tandem-heterodimer subunits, we determined that this potentiation also depends on the number of S4-S5 linkers and PVAV mutations in the K(v) channel tetramer. Consistent with the critical contribution of the Shaw2 S4-S5 linker, the equivalent PVAV mutation in certain mammalian K(v) channels with divergent S4-S5 linkers conferred weak potentiation by 1-butanol. Overall, these results suggest that 1-alkanol action in Shaw2 channels depends on interactions involving the S4-S5 linker and the S6-b segment. Therefore, we propose that amphiphilic general anesthetic agents such as 1-alkanols may modulate gating of the Shaw2 K(+) channel by an interaction with its activation gate." @default.
• W2121707070 created "2016-06-24" @default.
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• W2121707070 date "2006-08-03" @default.
• W2121707070 modified "2023-10-06" @default.
• W2121707070 title "The Concerted Contribution of the S4-S5 Linker and the S6 Segment to the Modulation of a K_v Channel by 1-Alkanols" @default.
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• W2121707070 doi "https://doi.org/10.1124/mol.106.026187" @default.
• W2121707070 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2211275" @default.
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