title: Do lipids show state-dependent affinity to the voltage-gated potassium channel KvAP?
abstract: As all integral membrane proteins, voltage-gated ion channels are embedded in a lipid matrix that regulates their channel behavior either by physicochemical properties or by direct binding. Because manipulation of the lipid composition in cells is difficult, we investigated the influence of different lipids on purified KvAP channels reconstituted in planar lipid bilayers of known composition. Lipids developed two distinct and independent effects on the KvAP channels; lipids interacting with the pore lowered the energy barriers for the final transitions, whereas voltage sensor-bound lipids shifted the midpoint of activation dependent on their electrostatic charge. Above all, the midpoint of activation was determined only by those lipids the channels came in contact with first after purification and can seemingly only be exchanged if the channel resides in the open state. The high affinity of the bound lipids to the binding site has implications not only on our understanding of the gating mechanism but also on the general experimental design of any lipid dependence study.
authors.affiliation: Groupe d'étude des protéines membranaires (GÉPROM), Université de Montréal, Montréal CH3C 3J7, Canada Physiology.
authors.forename: Élise
authors.initials: É
authors.lastname: Faure
authors.affiliation: Groupe d'étude des protéines membranaires (GÉPROM), Université de Montréal, Montréal CH3C 3J7, CanadaFrom the Departments of Physics and.
authors.forename: Christine
authors.initials: C
authors.lastname: Thompson
authors.affiliation: Groupe d'étude des protéines membranaires (GÉPROM), Université de Montréal, Montréal CH3C 3J7, Canada Physiology, From the Departments of Physics and rikard.blunck@umontreal.ca.
authors.forename: Rikard
authors.initials: R
authors.lastname: Blunck
mesh_terms: D015640:Ion Channel Gating; D050356:Lipid Metabolism; D015221:Potassium Channels / Q000502:physiology*
chemical_list: D015221:Potassium Channels
keywords: DOTAP; Electrophysiology; Gating; Ion Channel; Lipid Regulation; Membrane Reconstitution; Potassium Channel; Voltage-gated Potassium Channel
references.citation: Biochim Biophys Acta. 2011 Nov;1808(11):2761-71
references.pmid: 21819968
references.citation: Front Pharmacol. 2012 Sep 12;3:166
references.pmid: 22988442
references.citation: J Biol Chem. 2010 Apr 30;285(18):14005-19
references.pmid: 20202932
references.citation: J Gen Physiol. 1999 Mar;113(3):389-414
references.pmid: 10051516
references.citation: Biophys J. 2010 Feb 3;98(3):396-403
references.pmid: 20141752
references.citation: J Mol Biol. 2012 Nov 2;423(4):632-47
references.pmid: 22858867
references.citation: J Mol Biol. 2009 Jul 31;390(5):902-12
references.pmid: 19481093
references.citation: J Immunol. 2001 Jan 15;166(2):1009-15
references.pmid: 11145680
references.citation: J Gen Physiol. 2011 Jun;137(6):563-77
references.pmid: 21624947
references.citation: Nat Struct Mol Biol. 2009 Oct;16(10):1080-5
references.pmid: 19783984
references.citation: Biochim Biophys Acta. 1997 Oct 23;1329(2):211-22
references.pmid: 9371413
references.citation: Science. 1992 Mar 27;255(5052):1712-5
references.pmid: 1553560
references.citation: J Gen Physiol. 1998 Feb;111(2):313-42
references.pmid: 9450946
references.citation: J Am Chem Soc. 2013 Mar 13;135(10):3983-8
references.pmid: 23425320
references.citation: Science. 2005 Aug 5;309(5736):897-903
references.pmid: 16002581
references.citation: Nat Commun. 2011;2:250
references.pmid: 21427721
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15059-64
references.pmid: 16217012
references.citation: Science. 2004 Oct 15;306(5695):491-5
references.pmid: 15486302
references.citation: J Phys Chem B. 2007 Sep 6;111(35):10357-64
references.pmid: 17696389
references.citation: Curr Pharm Des. 2006;12(28):3631-44
references.pmid: 17073664
references.citation: J Gen Physiol. 2005 Jan;125(1):57-69
references.pmid: 15623895
references.citation: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8272-7
references.pmid: 23630265
references.citation: Nature. 2011 Jul 10;475(7356):353-8
references.pmid: 21743477
references.citation: J Physiol. 2011 Feb 1;589(Pt 3):461-79
references.pmid: 21098008
references.citation: Nature. 2008 Feb 14;451(7180):826-9
references.pmid: 18273018
references.citation: Nature. 2006 Dec 7;444(7120):775-9
references.pmid: 17136096
references.citation: J Gen Physiol. 2013 Oct;142(4):367-80
references.pmid: 24043861
references.citation: Science. 2012 Apr 13;336(6078):229-33
references.pmid: 22499946
references.citation: Nature. 2009 Nov 26;462(7272):473-9
references.pmid: 19940918
references.citation: J Gen Physiol. 1998 Mar;111(3):399-420
references.pmid: 9482708
references.citation: Biophys J. 2008 Sep;95(5):2242-53
references.pmid: 18502799
references.citation: J Am Chem Soc. 2013 May 8;135(18):6853-9
references.pmid: 23391155
references.citation: Nature. 2006 Aug 10;442(7103):696-9
references.pmid: 16799569
references.citation: J Biol Chem. 2012 Nov 16;287(47):40091-8
references.pmid: 23019337
references.citation: Biophys J. 2003 Sep;85(3):1734-40
references.pmid: 12944288
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):13008-13
references.pmid: 23882077
references.citation: J Gen Physiol. 2010 Nov;136(5):497-513
references.pmid: 20974771
references.citation: Nature. 2007 Nov 15;450(7168):376-82
references.pmid: 18004376
references.citation: Nature. 2012 May 20;486(7401):135-9
references.pmid: 22678296
references.citation: J Gen Physiol. 1994 Feb;103(2):279-319
references.pmid: 8189207