Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, α-linolenic acid

Guizy, Miriam; David, Miren; Arias, C.; Zhang, Lian; Cofán, Montserrat; Ruı́z-Gutı́errez, Valentina; Ros, Emilio; Lillo, M. Pilar; Martens, Jeffrey R.; Valenzuela, Carmen

doi:10.1016/j.yjmcc.2007.11.004

Cited by 38 publications

(42 citation statements)

References 55 publications

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“…The inhibition action of these FFA on HERG channels can help to further explain the reported antiarrhythmic effects of AA and/or DHA (Guizy et al, 2005). Open-channel blockage by polyunsaturated FFA, apparently by binding of the FFA to an external site in the channel, was also reported for the major voltage-dependent K + channel (Kv1.5) cloned from cardiac cells (Honoré et al, 1994; Guizy et al, 2008). In contrast to this effect, Gavrilova-Ruch et al (2007) reported that AA activated human ether à go-go (hEAG) potassium channels expressed in CHO cells, an effect totally reversed upon washing with BSA.…”

Section: Ffa Effects On Voltage-gated Ion Channelsmentioning

confidence: 64%

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Antollini

Barrantes

2016

Front. Physiol.

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Free fatty acids (FFA) are essential components of the cell, where they play a key role in lipid and carbohydrate metabolism, and most particularly in cell membranes, where they are central actors in shaping the physicochemical properties of the lipid bilayer and the cellular adaptation to the environment. FFA are continuously being produced and degraded, and a feedback regulatory function has been attributed to their turnover. The massive increase observed under some pathological conditions, especially in brain, has been interpreted as a protective mechanism possibly operative on ion channels, which in some cases is of stimulatory nature and in other cases inhibitory. Here we discuss the correlation between the structure of FFA and their ability to modulate protein function, evaluating the influence of saturation/unsaturation, number of double bonds, and cis vs. trans isomerism. We further focus on the mechanisms of FFA modulation operating on voltage-gated and ligand-gated ion channel function, contrasting the still conflicting evidence on direct vs. indirect mechanisms of action.

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Section: Ffa Effects On Voltage-gated Ion Channelsmentioning

confidence: 64%

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Antollini

Barrantes

2016

Front. Physiol.

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“…Wu et al [11] demonstrated that the enhancement of outward voltage-gated K + (IK V ) currents and inwardly rectifying IK 1 currents could be related to vasorelaxation induced by DHA in human coronary artery smooth muscle, and Poling et al [10] reported that DHA inhibited K V channels in neurons. Studies have also shown that DHA inhibits K V channels in ventricular myocytes, in which the expression of K V 1.1-K V 1.5 and K V 4.1-K V 4.2 has been detected [32,33] . Our studies have shown that DHA at concentrations greater than 20 µmol/L markedly inhibited K V channels in rat CASMCs.…”

Section: Discussionmentioning

confidence: 99%

Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells

et al. 2009

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Aim:To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca 2+ -activated K + (BK Ca ) channels and voltage-dependent K + (K V ) channels in rat coronary artery smooth muscle cells (CASMCs) . Methods: Rat CASMCs were isolated by an enzyme digestion method. BK Ca and K V currents in individual CASMCs were recorded by the patch-clamp technique in a whole-cell configuration at room temperature. Effects of DHA on BK Ca and K V channels were observed when it was applied at 10,20,30, 40, 50, 60, 70, and 80 µmol/L. Results: When DHA concentrations were greater than 10 µmol/L, BK Ca currents increased in a dose-dependent manner. At a testing potential of +80 mV, 6.1%±0.3%, 76.5%±3.8%, 120.6%±5.5%, 248.0%±12.3%, 348.7%±17.3%, 374.2%±18.7%, 432.2%±21.6%, and 443.1%±22.1% of BK Ca currents were increased at the above concentrations, respectively. The half-effective concentration (EC 50 ) of DHA on BK Ca currents was 37.53±1.65 µmol/L. When DHA concentrations were greater than 20 µmol/L, K V currents were gradually blocked by increasing concentrations of DHA. At a testing potential of +50 mV, 0.40%±0.02%, 1.37%±0.06%, 11.80%±0.59%, 26.50%±1.75%, 56.50%±2.89%, 73.30%±3.66%, 79.70%±3.94%, and 78.1%±3.91% of K V currents were blocked at the different concentrations listed above, respectively. The EC 50 of DHA on K V currents was 44.20±0.63 µmol/L. Conclusions: DHA can activate BK Ca channels and block K V channels in rat CASMCs, and the EC 50 of DHA for BK Ca channels is lower than that for K V channels; these findings indicate that the vasorelaxation effects of DHA on vascular smooth muscle cells are mainly due to its activation of BK Ca channels.

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“…DHA inhibits K v 1.2 channels extracellularly (40), and linoleic acid modulates K v 2.1 from the extracellular side (34). Similarly, the inhibitory effects of ␣-linolenic acid, arachidonic acid, DHA, and linoleic acid on K v 1.5 channels are externally mediated (21,23,34). In contrast, the arachidonic acid derivative anandamide inhibits K v 1.5 channels via an intracellular pore block mechanism (36).…”

Section: Mechanism Of Action Of Pufas On C-type Inactivationmentioning

confidence: 99%

“…A number of previous studies have investigated the effects of PUFAs on K v channels (21,23,34,40,43,48,48); however, the site and mechanism of action of PUFAs are uncertain. DHA inhibits K v 1.2 channels, an effect that has been ascribed to external block (40), while linoleic acid modulates K v 2.1 from the extracellular side (34).…”

mentioning

confidence: 99%

Polyunsaturated fatty acids inhibit K_v1.4 by interacting with positively charged extracellular pore residues

Farag

Jeong

Claydon

et al. 2016

American Journal of Physiology-Cell Physiology

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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.

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Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, α-linolenic acid

Cited by 38 publications

References 55 publications

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells

Polyunsaturated fatty acids inhibit K_v1.4 by interacting with positively charged extracellular pore residues

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Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, α-linolenic acid

Cited by 38 publications

References 55 publications

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Fatty Acid Regulation of Voltage- and Ligand-Gated Ion Channel Function

Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells

Polyunsaturated fatty acids inhibit Kv1.4 by interacting with positively charged extracellular pore residues

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Polyunsaturated fatty acids inhibit K_v1.4 by interacting with positively charged extracellular pore residues