scholarly journals Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels

2009 ◽  
Vol 296 (5) ◽  
pp. C1003-C1014 ◽  
Author(s):  
Linda M. Boland ◽  
Michelle M. Drzewiecki ◽  
Gabriela Timoney ◽  
Erin Casey
Keyword(s):  
Fatty Acids ◽  
Potassium Channels ◽  
Polyunsaturated Fatty Acids ◽  
Time Course ◽  
Expression System ◽  
K Channel ◽  
Xenopus Laevis Oocyte ◽  
Inhibitory Effects ◽  
Interacting Protein ◽  
Steady State Inactivation

Kv4/K channel interacting protein (KChIP) potassium channels are a major class of rapidly inactivating K+ channels in neurons and cardiac muscle. Modulation of Kv4/KChIP channels by polyunsaturated fatty acids (PUFAs) is important in the regulation of cellular excitability and the induction of activity-dependent synaptic plasticity. Using the Xenopus laevis oocyte expression system, we studied the inhibition by PUFAs of the peak outward K+ current and the accompanying increase in the rate of current inactivation of rKv4.2/rKChIP1b. Inhibitory effects do not depend on KChIP coexpression since Kv4.2 channels lacking an NH2-terminal KChIP association region were substantially inhibited by PUFAs and showed strong kinetic modulation. PUFAs accelerated both the fast and slow time constants that describe the kinetics of Kv4/KChIP inactivation. The time course of entry into closed inactivated states was facilitated by PUFAs, but steady-state inactivation and recovery from inactivation were unaltered. PUFA inhibition of Kv4/KChIP current was not use dependent. The concentration-response relationship for arachidonic acid (AA) inhibition of Kv4/KChIP channels mimicked that for activation of TRAAK channels. Internal serum albumin largely prevents the inhibitory effects of externally applied AA, and the membrane-impermeant AA-CoA is inactive when applied externally. Overall, our data suggest that PUFAs inhibit Kv4/KChIP channels by facilitating inactivation from open and closed gating states and that access of the fatty acid to the internal leaflet of the membrane is important. These results improve our understanding of the mechanisms for the inhibitory effects of PUFAs on Kv4/KChIP channel function.

Time course of incorporation of n-3 PUFA from linseed in pigs and effects on D9-desaturase activity and pork odours

2001 ◽  
Vol 2001 ◽  
pp. 71-71
Author(s):  
M. Kouba ◽  
M. Enser ◽  
G.R. Nute ◽  
F.M. Whittington ◽  
J.D. Wood ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Polyunsaturated Fatty Acids ◽  
Time Course ◽  
Desaturase Activity ◽  
Monounsaturated Fatty Acids ◽  
Lipid Classes ◽  
Inhibitory Effects ◽  
Tissue Lipids ◽  
Feeding Sources

The n-3 polyunsaturated fatty acids (PUFA) are healthy nutrients which can be increased in pork by feeding sources such as linseed to the growing animal. The levels achieved depend on many factors such as the concentrations of lipid classes in tissues (eg phospholipids containing high PUFA levels are more abundant in muscle than adipose tissue) competition for incorporation with n-6 PUFA and possible inhibitory effects of PUFA on synthesis of saturated and monounsaturated fatty acids. This study examined the time course of the incorporation of n-3 PUFA into tissue lipids and the effects on the major synthetic enzyme D9-desaturase. The effects on pork odour were also studied.

scholarly journals Convergence of Multiple Stimuli to a Single Gate in TREK1 and TRAAK Potassium Channels

2021 ◽  
Vol 12 ◽  
Author(s):  
Frank S Choveau ◽  
Ismail Ben Soussia ◽  
Delphine Bichet ◽  
Chatelain C. Franck ◽  
Sylvain Feliciangeli ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Potassium Channels ◽  
Polyunsaturated Fatty Acids ◽  
Extracellular Ph ◽  
Channel Activity ◽  
Membrane Stretch ◽  
State Dependent ◽  
The Subject ◽  
Intense Research

Inhibitory potassium channels of the TREK1/TRAAK family are integrators of multiple stimuli, including temperature, membrane stretch, polyunsaturated fatty acids and pH. How these signals affect the gating of these channels is the subject of intense research. We have previously identified a cytoplasmic domain, pCt, which plays a major role in controlling channel activity. Here, we use pharmacology to show that the effects of pCt, arachidonic acid, and extracellular pH converge to the same gate within the channel. Using a state-dependent inhibitor, fluoxetine, as well as natural and synthetic openers, we provide further evidence that the “up” and “down” conformations identified by crystallography do not correspond to open and closed states of these channels.

Full-length and truncated Kv1.3 K+ channels are modulated by 5-HT1c receptor activation and independently by PKC

1993 ◽  
Vol 265 (6) ◽  
pp. C1571-C1578 ◽  
Author(s):  
J. Aiyar ◽  
S. Grissmer ◽  
K. G. Chandy
Keyword(s):  
G Protein ◽  
Time Course ◽  
Phorbol Esters ◽  
Expression System ◽  
Receptor Activation ◽  
K Channel ◽  
Dependent Manner ◽  
Phosphatase Inhibitors ◽  
Kv1.3 Channel ◽  
Subsequent Rise

In T-cells, the Shaker-related gene, Kv1.3 encodes the type n K+ channel, whereas the type l channel is a product of the Shaw. subfamily gene, Kv3.1. Both these genes are also expressed in the brain. We have used the Xenopus oocyte heterologous expression system to study the modulatory effects of serotonin (5-hydroxytryptamine, 5-HT) on both these cloned channels. In oocytes coexpressing the mouse 5-HT1c receptor and mouse Kv1.3 channel, addition of 100 nM 5-HT causes a complete and sustained suppression of Kv1.3 currents in approximately 20 min. In contrast, 5-HT has no effect on mouse Kv3.1 currents when coexpressed with 5-HT1c receptor. The 5-HT-mediated suppression of Kv1.3 currents proceeds via activation of a pertussis toxin-sensitive G protein and a subsequent rise in intracellular Ca2+, but Ca2+ does not directly block the channel. Protein kinase (PK) C activation is not part of the pathway linking 5-HT1c receptor to Kv1.3 channels. However, phorbol esters independently suppress Kv1.3 currents. Deletion of the first 146 amino acids from the NH2-terminal, containing putative tyrosine kinase and PKA phosphorylation sites, does not alter the time course of 5-HT-mediated suppression of Kv1.3 currents, indicating that these residues are not necessary for modulation. Treatment of oocytes with calmodulin or phosphatase inhibitors does not alter 5-HT-mediated modulation. Collectively, these experiments indicate that the mouse Kv1.3 channel is capable of being modulated by 5-HT via 5-HT1c receptor in a G protein and Ca(2+)-dependent manner, but the subsequent steps in the pathway remain elusive.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito

2004 ◽  
Vol 286 (2) ◽  
pp. H602-H609 ◽  
Author(s):  
Fadi G. Akar ◽  
Richard C. Wu ◽  
Isabelle Deschenes ◽  
Antonis A. Armoundas ◽  
Valentino Piacentino ◽  
...  
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Phenotypic Expression ◽  
Functional Expression ◽  
K Channel ◽  
Inactivation Kinetics ◽  
Phenotypic Properties ◽  
Interacting Protein ◽  
Phenotypic Differences ◽  
Recovery From Inactivation

The Ca2+-independent transient outward K+ current ( Ito) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of Ito. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular Ito of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine Ito. Whereas recovery from inactivation of human Ito followed a monoexponential time course, canine Ito recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine Ito, and exposure to oxidative stress did not alter the inactivation kinetics of Ito in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular Ito despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of Ito between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode Ito, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits.

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