Subtype specific responses in hKv7.4 and hKv7.5 channels to polyunsaturated fatty acids

The KV7.4 and KV7.5 subtypes of voltage-gated potassium channels are expressed in several tissues where they play a role in physiological processes such as sound amplification in the cochlea and adjusting vascular smooth muscle tone. Therefore, the mechanisms that regulate KV7.4 and KV7.5 channel function are of interest. Here, we study the effect of polyunsaturated fatty acids (PUFAs) on human KV7.4 and KV7.5 channels expressed in Xenopus oocytes. We report that KV7.5 is activated by PUFAs, which shift the V50 of the conductance versus voltage (G(V)) curve towards more negative voltages. This response depends on the charge of the head group as an uncharged PUFA analogue has no effect and a positively charged PUFA analogue induces positive V50 shifts. In contrast, we find that the KV7.4 channel is inhibited by PUFAs, which shift V50 towards more positive voltages. No effect on V50 of KV7.4 is observed by an uncharged or a positively charged PUFA analogue. Oocytes co-expressing KV7.4 and KV7.5 display an intermediate response to PUFAs. Altogether, the KV7.5 channel's response to PUFAs is like that previously observed in KV7.1-7.3 channels, whereas the KV7.4 channel response is opposite, revealing subtype specific responses to PUFAs.

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

AJP Cell Physiology ◽

10.1152/ajpcell.00277.2015 ◽

2016 ◽

Vol 311 (2) ◽

pp. C255-C268 ◽

Cited By ~ 5

Author(s):

N. E. Farag ◽

D. Jeong ◽

T. Claydon ◽

J. Warwicker ◽

M. R. Boyett

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Head Group ◽

Interaction Sites ◽

Channel Inactivation ◽

Recovery From Inactivation ◽

Sensor Activation ◽

Separable Interaction ◽

Positively Charged ◽

Charge Calculations

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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Effects of omega-3, omega-6 and omega-9 fatty acids on vascular smooth muscle tone

European Journal of Pharmacology ◽

10.1016/0014-2999(92)90050-e ◽

1992 ◽

Vol 215 (2-3) ◽

pp. 325-328 ◽

Cited By ~ 18

Author(s):

Mary B. Engler

Keyword(s):

Fatty Acids ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Tone ◽

Omega 3 ◽

Smooth Muscle Tone ◽

Omega 6 ◽

3 Omega ◽

Vascular Smooth Muscle Tone

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A range of activators for cardiac IKs channels

The Journal of General Physiology ◽

10.1085/jgp.201912557 ◽

2020 ◽

Vol 152 (2) ◽

Author(s):

Ben Short

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Long Qt Syndrome ◽

Head Group ◽

Long Qt ◽

Qt Syndrome

JGP study suggests that varying the head group of polyunsaturated fatty acids could enable personalized treatments for long QT syndrome.

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Enzymatic synthesis of new hepoxilins and trioxilins from polyunsaturated fatty acids

Green Chemistry ◽

10.1039/c9gc01031a ◽

2019 ◽

Vol 21 (11) ◽

pp. 3172-3181 ◽

Cited By ~ 4

Author(s):

In-Gyu Lee ◽

Jung-Ung An ◽

Yoon-Joo Ko ◽

Jin-Byung Park ◽

Deok-Kun Oh

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Enzymatic Synthesis ◽

Lipid Mediators ◽

Physiological Processes

Hepoxilins (HXs) and trioxilins (TrXs) are lipid mediators that regulate diverse physiological processes at trace amounts in humans.

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Polyunsaturated Fatty Acids (PUFAs) Might Reduce Hot Flushes: An Indication From Two Controlled Trials on Soy Isoflavones Alone and With a PUFA Supplement

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70555-1 ◽

2006 ◽

Vol 2006 ◽

pp. 385-387

Author(s):

L.P. Shulman

Keyword(s):

Fatty Acids ◽

Polyunsaturated Fatty Acids ◽

Soy Isoflavones ◽

Controlled Trials ◽

Hot Flushes ◽

Pufa Supplement

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A randomized, double-blind, placebo-controlled study of polyunsaturated fatty acids efficacy in adolescents with anorexia nervosa

Pharmacotherapy in Psychiatry and Neurology ◽

10.33450/fpn.2020.06.001 ◽

2020 ◽

Vol 36 (2) ◽

pp. 95-106

Author(s):

Agnieszka M. Piróg-Balcerzak ◽

Anna K. Bażyńska ◽

Katarzyna Biernacka ◽

Joanna Brągoszewska ◽

Lidia Popek ◽

...

Keyword(s):

Fatty Acids ◽

Anorexia Nervosa ◽

Polyunsaturated Fatty Acids ◽

Small Sample Size ◽

Small Sample ◽

Female Adolescent ◽

Eating Attitude ◽

Controlled Study ◽

Omega 3 ◽

Eat 26

Objective. Omega–3 polyunsaturated fatty acids (PUFAs) were tested in adolescent depression and in several neurodevelopmental disorders with partial success. Anorexia nervosa (AN) is characterised by deficiencies in fatty food intake and frequent comorbidity, including depressive and cognitive symptoms. Thus supplementation with PUFAs may be beneficial in this group of patients. The aim of the study was to assess whether PUFAs as an add-on treatment is associated with better improvement of body mass index (BMI) and psychopathological symptoms than placebo in patients with AN. Method. 61 female adolescent inpatients with AN were randomly allocated to omega–3 PUFAs supplementation or placebo for 10 weeks. Patients also participated in the behavioural programme and eclectic psychotherapy (treatment as usual, TAU). At baseline and follow-up visits, patients’ BMI and psychopathology were assessed with Clinical Global Impression Scale (CGI), Patient Global Impression Scale (PGI), and Eating Attitude Test (EAT-26). Results. After 10 weeks, both groups showed improvement in all parameters. Improvement in CGI scores was observed greater in placebo vs. PUFA-s group (p = 0.015) while other differences were not statistically significant. Omega–3 PUFAs supplementation appears not to be effective as an add-on treatment in inpatient adolescent girls with anorexia nervosa. Conclusions. The results should be analysed with caution due to small sample size and heterogeneity in TAU. As the TAU turned out to be highly effective, additional therapeutic effect of PUFA might not be visible. Nevertheless, that does not explain the tendency for better improvement in the placebo group.

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