Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes
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Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes. / Liin, Sara I; Karlsson, Urban; Bentzen, Bo Hjorth; Schmitt, Nicole; Elinder, Fredrik.
I: Acta Physiologica (Print), Bind 218, Nr. 1, 23.02.2016, s. 28-37.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 160457372