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Am J Physiol Cell Physiol
2016 Aug 01;3112:C255-68. doi: 10.1152/ajpcell.00277.2015.
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Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues.
Farag NE
,
Jeong D
,
Claydon T
,
Warwicker J
,
Boyett MR
.
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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 Kv1.4 channel. PUFAs inhibited wild-type Kv1.4 during repetitive pulsing as a result of slowing of recovery from inactivation. In a mutant Kv1.4 channel lacking N-type inactivation, PUFAs reversibly enhanced C-type inactivation (Kd, 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 pKa of H508 and this reduces the K(+) occupancy of the selectivity filter, stabilizing the C-type inactivated state.
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995, Pubmed
Baukrowitz,
Modulation of K+ current by frequency and external [K+]: a tale of two inactivation mechanisms.
1995,
Pubmed
Baukrowitz,
Use-dependent blockers and exit rate of the last ion from the multi-ion pore of a K+ channel.
1996,
Pubmed
Bhatnagar,
Beating ischemia: a new feat of EETs?
2004,
Pubmed
Billman,
Prevention of ischemia-induced ventricular fibrillation by omega 3 fatty acids.
1994,
Pubmed
Bogdanov,
Modulation of the transient outward current in adult rat ventricular myocytes by polyunsaturated fatty acids.
1998,
Pubmed
Börjesson,
Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids.
2008,
Pubmed
,
Xenbase
Börjesson,
An electrostatic potassium channel opener targeting the final voltage sensor transition.
2011,
Pubmed
,
Xenbase
Brahmajothi,
Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes.
1999,
Pubmed
Bringmann,
Alterations of potassium channel activity in retinal Müller glial cells induced by arachidonic acid.
1998,
Pubmed
Calon,
Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.
2005,
Pubmed
Chien,
Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids.
1984,
Pubmed
Claydon,
K+ activation of kir3.1/kir3.4 and kv1.4 K+ channels is regulated by extracellular charges.
2004,
Pubmed
,
Xenbase
Claydon,
Two pore residues mediate acidosis-induced enhancement of C-type inactivation of the Kv1.4 K(+) channel.
2002,
Pubmed
,
Xenbase
Claydon,
Inhibition of the K+ channel kv1.4 by acidosis: protonation of an extracellular histidine slows the recovery from N-type inactivation.
2000,
Pubmed
,
Xenbase
Das,
Long-chain polyunsaturated fatty acids in the growth and development of the brain and memory.
2003,
Pubmed
Fedida,
Synergistic inhibition of the maximum conductance of Kv1.5 channels by extracellular K+ reduction and acidification.
2005,
Pubmed
Gubitosi-Klug,
Concomitant acceleration of the activation and inactivation kinetics of the human delayed rectifier K+ channel (Kv1.1) by Ca(2+)-independent phospholipase A2.
1995,
Pubmed
Guex,
SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling.
1997,
Pubmed
Guizy,
{Omega}-3 and {omega}-6 polyunsaturated fatty acids block HERG channels.
2005,
Pubmed
Guizy,
Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, alpha-linolenic acid.
2008,
Pubmed
Holmqvist,
Kinetic modulation of Kv4-mediated A-current by arachidonic acid is dependent on potassium channel interacting proteins.
2001,
Pubmed
,
Xenbase
Honoré,
External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids.
1994,
Pubmed
Keros,
Arachidonic acid inhibits transient potassium currents and broadens action potentials during electrographic seizures in hippocampal pyramidal and inhibitory interneurons.
1997,
Pubmed
Klemic,
U-type inactivation of Kv3.1 and Shaker potassium channels.
2001,
Pubmed
,
Xenbase
Klemic,
Inactivation of Kv2.1 potassium channels.
1998,
Pubmed
,
Xenbase
Kris-Etherton,
Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.
2002,
Pubmed
Li,
Regulation of N- and C-type inactivation of Kv1.4 by pHo and K+: evidence for transmembrane communication.
2003,
Pubmed
,
Xenbase
Liin,
Polyunsaturated fatty acid analogs act antiarrhythmically on the cardiac IKs channel.
2015,
Pubmed
,
Xenbase
Liu,
Modelling the pH-dependent properties of Kv1 potassium channels.
2007,
Pubmed
Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed
López-Barneo,
Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels.
1993,
Pubmed
,
Xenbase
McKay,
Linoleic acid both enhances activation and blocks Kv1.5 and Kv2.1 channels by two separate mechanisms.
2001,
Pubmed
Meves,
Modulation of ion channels by arachidonic acid.
1994,
Pubmed
Moreno-Galindo,
Molecular basis for a high-potency open-channel block of Kv1.5 channel by the endocannabinoid anandamide.
2010,
Pubmed
Nelson,
Isolation of a G protein that is modified by learning and reduces potassium currents in Hermissenda.
1990,
Pubmed
Ogielska,
Functional consequences of a decreased potassium affinity in a potassium channel pore. Ion interactions and C-type inactivation.
1999,
Pubmed
,
Xenbase
Oliver,
Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.
2004,
Pubmed
,
Xenbase
Poling,
Docosahexaenoic acid block of neuronal voltage-gated K+ channels: subunit selective antagonism by zinc.
1996,
Pubmed
Rasmusson,
C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.
1995,
Pubmed
,
Xenbase
Siddiqui,
Modulation of enzymatic activities by n-3 polyunsaturated fatty acids to support cardiovascular health.
2008,
Pubmed
Singleton,
Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells.
1999,
Pubmed
Smirnov,
Modulatory effects of arachidonic acid on the delayed rectifier K+ current in rat pulmonary arterial myocytes. Structural aspects and involvement of protein kinase C.
1996,
Pubmed
Somodi,
Effects of changes in extracellular pH and potassium concentration on Kv1.3 inactivation.
2008,
Pubmed
Steidl,
Differential sensitivity of voltage-gated potassium channels Kv1.5 and Kv1.2 to acidic pH and molecular identification of pH sensor.
1999,
Pubmed
,
Xenbase
Trimmer,
Localization of voltage-gated ion channels in mammalian brain.
2004,
Pubmed
Villarroel,
Inhibition of the Kv4 (Shal) family of transient K+ currents by arachidonic acid.
1996,
Pubmed
,
Xenbase
Warwicker,
Improved pKa calculations through flexibility based sampling of a water-dominated interaction scheme.
2004,
Pubmed
Xiao,
Effects of polyunsaturated fatty acids on cardiac voltage-activated K(+) currents in adult ferret cardiomyocytes .
2002,
Pubmed
