title: Polyunsaturated fatty acids are potent openers of human M-channels expressed in Xenopus laevis oocytes.
abstract: 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 neurones.
  
  
  
  Effects of fatty acids and fatty acid analogues on mouse dorsal root ganglion neurones and on the human KV 7.2/3 channel expressed in Xenopus laevis oocytes were studied using electrophysiology.
  
  
  
  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 neurones. 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-vs.-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.
  
  
  
  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.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: S I
authors.identifier: 0000-0001-8493-0114
authors.initials: SI
authors.lastname: Liin
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Karlsson
authors.affiliation: Department of Biomedical Sciences, Danish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B H
authors.initials: BH
authors.lastname: Bentzen
authors.affiliation: Department of Biomedical Sciences, Danish National Research Foundation Centre for Cardiac Arrhythmia, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Schmitt
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Elinder
mesh_terms: D000818:Animals; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D051658:KCNQ2 Potassium Channel / Q000819:agonists*; D051659:KCNQ3 Potassium Channel / Q000819:agonists*; D008564:Membrane Potentials / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D014982:Xenopus laevis
chemical_list: D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human; D051659:KCNQ3 Potassium Channel; C496916:KCNQ3 protein, human
keywords: KCNQ potassium channel family; M-channel; electrophysiology; epilepsy; excitability; polyunsaturated fatty acids