TY - JOUR

T1 - Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes

AU - Liin, Sara I

AU - Karlsson, Urban

AU - Bentzen, Bo Hjorth

AU - Schmitt, Nicole

AU - Elinder, Fredrik

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/2/23

Y1 - 2016/2/23

N2 - AIM: Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurons.METHODS: Effects of fatty acids and fatty-acid analogues on mouse dorsal root ganglion neurons and on the human KV 7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology.RESULTS: Extracellular application of physiologically relevant concentrations of the polyunsaturated fatty acid docosahexaenoic acid hyperpolarized the resting membrane potential (-2.4 mV by 30 μM) and increased the threshold current to evoke action potentials in dorsal root ganglion neurons. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes, by shifting the conductance-versus-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μM). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel.CONCLUSIONS: These findings suggest that circulating polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty acids reduce neuronal excitability. This article is protected by copyright. All rights reserved.

AB - AIM: Polyunsaturated fatty acids have been reported to reduce neuronal excitability, in part by promoting inactivation of voltage-gated sodium and calcium channels. Effects on neuronal potassium channels are less explored and experimental data ambiguous. The aim of this study was to investigate anti-excitable effects of polyunsaturated fatty acids on the neuronal M-channel, important for setting the resting membrane potential in hippocampal and dorsal root ganglion neurons.METHODS: Effects of fatty acids and fatty-acid analogues on mouse dorsal root ganglion neurons and on the human KV 7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology.RESULTS: Extracellular application of physiologically relevant concentrations of the polyunsaturated fatty acid docosahexaenoic acid hyperpolarized the resting membrane potential (-2.4 mV by 30 μM) and increased the threshold current to evoke action potentials in dorsal root ganglion neurons. The polyunsaturated fatty acids docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid facilitated opening of the human M-channel, comprised of the heteromeric human KV 7.2/3 channel expressed in Xenopus oocytes, by shifting the conductance-versus-voltage curve towards more negative voltages (by -7.4 to -11.3 mV by 70 μM). Uncharged docosahexaenoic acid methyl ester and monounsaturated oleic acid did not facilitate opening of the human KV 7.2/3 channel.CONCLUSIONS: These findings suggest that circulating polyunsaturated fatty acids, with a minimum requirement of multiple double bonds and a charged carboxyl group, dampen excitability by opening neuronal M-channels. Collectively, our data bring light to the molecular targets of polyunsaturated fatty acids and thus a possible mechanism by which polyunsaturated fatty acids reduce neuronal excitability. This article is protected by copyright. All rights reserved.

U2 - 10.1111/apha.12663

DO - 10.1111/apha.12663

M3 - Journal article

C2 - 26914447

VL - 218

SP - 28

EP - 37

JO - Acta Physiologica

JF - Acta Physiologica

SN - 1748-1708

IS - 1

ER -