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- W2414835306 abstract "Polyunsaturated fatty acids (PUFAs) modulate voltage-gated K + channel inactivation by an unknown site and mechanism. The effects of ω-6 and ω-3 PUFAs were investigated on the heterologously expressed K v 1.4 channel. PUFAs inhibited wild-type K v 1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant K v 1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation ( K d , 15–43 μM). C-type inactivation was affected by extracellular H + and K + as well as PUFAs and there was an interaction among the three: the effect of PUFAs was reversed during acidosis and abolished on raising K + . Replacement of two positively charged residues in the extracellular pore (H508 and K532) abolished the effects of the PUFAs (and extracellular H + and K + ) on C-type inactivation but had no effect on the lipoelectric modulation of voltage sensor activation, suggesting two separable interaction sites/mechanisms of action of PUFAs. Charge calculations suggest that the acidic head group of the PUFAs raises the pK a of H508 and this reduces the K + occupancy of the selectivity filter, stabilizing the C-type inactivated state." @default.
- W2414835306 created "2016-06-24" @default.
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- W2414835306 date "2016-08-01" @default.
- W2414835306 modified "2023-09-27" @default.
- W2414835306 title "Polyunsaturated fatty acids inhibit K<sub>v</sub>1.4 by interacting with positively charged extracellular pore residues" @default.
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- W2414835306 doi "https://doi.org/10.1152/ajpcell.00277.2015" @default.
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