Effects of n-3 polyunsaturated fatty acids on cardiac ion channels

Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on cardiac sodium channel (Nav1.5) and two potassium channels (Kv) (Kv1.5 and...

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Main Authors: Cristina eMoreno, Alvaro eMacias, Angela ePrieto, Alicia ede la Cruz, Teresa eGonzalez, Carmen eValenzuela
Format: Article
Language:English
Published: Frontiers Media S.A. 2012-07-01
Series:Frontiers in Physiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00245/full
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author Cristina eMoreno
Alvaro eMacias
Angela ePrieto
Alicia ede la Cruz
Teresa eGonzalez
Carmen eValenzuela
author_facet Cristina eMoreno
Alvaro eMacias
Angela ePrieto
Alicia ede la Cruz
Teresa eGonzalez
Carmen eValenzuela
author_sort Cristina eMoreno
collection DOAJ
description Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on cardiac sodium channel (Nav1.5) and two potassium channels (Kv) (Kv1.5 and Kv11.1). n-3 marine (docohexaenoic and eicohexapentaenoic acid) and plant origin (alpha-linolenic acid) PUFAs block Kv1.5 and Kv11.1 channels at physiological concentrations. Also, DHA and EPA decreased Nav1.5 and calcium channels. These effects on Na and Ca channels theoretically should shorten the cardiac APD, whereas the blocking actions of n-3 PUFAs of Kv channels should lengthen the cardiac action potential. Experiments performed in female rabbits fed with a diet rich in n-3 PUFAs show a longer cardiac action potential and effective refractory period. This study was performed to analyze if their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability and dispersion of the cardiac action potential (TRIaD as a measure of proarrhythmic effects). Dietary n-3 PUFAs supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced torsades de pointes (TdP). Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of dietary supplements of n-3 PUFAs against dofetilide induced proarrhythmia observed in this animal model. The cardiac effects of n-3 PUFAs resemble those of amiodarone: both block sodium, calcium and potassium channels, have anti-adrenergic properties, can prolong the cardiac action potential, reverse TRIaD and suppress TdP. The main difference is that sodium channel block by n-3 PUFAs has a much faster onset and offset kinetics. Therefore, the electrophysiological profile of n-3 PUFAs appears more desirable: the duration of reduced sodium current (facilitates re-entry) is much shorter. The n-3 PUFAs appear as a safer alternative to other antiarrhythmic agents.
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spelling doaj.art-523695a8f97b4a5da69b3190f3ae23d92022-12-22T00:55:34ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2012-07-01310.3389/fphys.2012.0024525629Effects of n-3 polyunsaturated fatty acids on cardiac ion channelsCristina eMoreno0Alvaro eMacias1Angela ePrieto2Alicia ede la Cruz3Teresa eGonzalez4Carmen eValenzuela5Instituto de Investigaciones Biomédicas CSIC-UAMInstituto de Investigaciones Biomédicas CSIC-UAMInstituto de Investigaciones Biomédicas CSIC-UAMInstituto de Investigaciones Biomédicas CSIC-UAMInstituto de Investigaciones Biomédicas CSIC-UAMInstituto de Investigaciones Biomédicas CSIC-UAMDietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, attributed to their capability to modulate ion channels. In the present review, we will focus on the effects of PUFAs on cardiac sodium channel (Nav1.5) and two potassium channels (Kv) (Kv1.5 and Kv11.1). n-3 marine (docohexaenoic and eicohexapentaenoic acid) and plant origin (alpha-linolenic acid) PUFAs block Kv1.5 and Kv11.1 channels at physiological concentrations. Also, DHA and EPA decreased Nav1.5 and calcium channels. These effects on Na and Ca channels theoretically should shorten the cardiac APD, whereas the blocking actions of n-3 PUFAs of Kv channels should lengthen the cardiac action potential. Experiments performed in female rabbits fed with a diet rich in n-3 PUFAs show a longer cardiac action potential and effective refractory period. This study was performed to analyze if their antiarrhythmic effects are due to a reduction of triangulation, reverse use-dependence, instability and dispersion of the cardiac action potential (TRIaD as a measure of proarrhythmic effects). Dietary n-3 PUFAs supplementation markedly reduced dofetilide-induced TRIaD and abolished dofetilide-induced torsades de pointes (TdP). Ultrafast sodium channel block by DHA may account for the antiarrhythmic protection of dietary supplements of n-3 PUFAs against dofetilide induced proarrhythmia observed in this animal model. The cardiac effects of n-3 PUFAs resemble those of amiodarone: both block sodium, calcium and potassium channels, have anti-adrenergic properties, can prolong the cardiac action potential, reverse TRIaD and suppress TdP. The main difference is that sodium channel block by n-3 PUFAs has a much faster onset and offset kinetics. Therefore, the electrophysiological profile of n-3 PUFAs appears more desirable: the duration of reduced sodium current (facilitates re-entry) is much shorter. The n-3 PUFAs appear as a safer alternative to other antiarrhythmic agents.http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00245/fullAtrial FibrillationHeart FailureIon Channelsarrhythmiasn-3 PUFAs
spellingShingle Cristina eMoreno
Alvaro eMacias
Angela ePrieto
Alicia ede la Cruz
Teresa eGonzalez
Carmen eValenzuela
Effects of n-3 polyunsaturated fatty acids on cardiac ion channels
Frontiers in Physiology
Atrial Fibrillation
Heart Failure
Ion Channels
arrhythmias
n-3 PUFAs
title Effects of n-3 polyunsaturated fatty acids on cardiac ion channels
title_full Effects of n-3 polyunsaturated fatty acids on cardiac ion channels
title_fullStr Effects of n-3 polyunsaturated fatty acids on cardiac ion channels
title_full_unstemmed Effects of n-3 polyunsaturated fatty acids on cardiac ion channels
title_short Effects of n-3 polyunsaturated fatty acids on cardiac ion channels
title_sort effects of n 3 polyunsaturated fatty acids on cardiac ion channels
topic Atrial Fibrillation
Heart Failure
Ion Channels
arrhythmias
n-3 PUFAs
url http://journal.frontiersin.org/Journal/10.3389/fphys.2012.00245/full
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