Polyunsaturated Fatty Acids Modify the Gating of Kv Channels

Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will foc...

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Main Authors:	Moreno, Cristina, Macias, Alvaro, Prieto, Angela, De La Cruz, Alicia, Valenzuela, Carmen
Format:	Online
Language:	English
Published:	Frontiers Research Foundation 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437463/

id	pubmed-3437463
recordtype	oai_dc
spelling	pubmed-34374632012-09-12 Polyunsaturated Fatty Acids Modify the Gating of Kv Channels Moreno, Cristina Macias, Alvaro Prieto, Angela De La Cruz, Alicia Valenzuela, Carmen Pharmacology Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are blocked by n−3 PUFAs of marine [docosahexaenoic acid (DHA) and eicosapentaenoic acid] and plant origin (alpha-linolenic acid, ALA) at physiological concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the range of membrane potentials coinciding with those of Kv1.5 channel activation, suggesting that PUFAs-channel binding may derive a significant fraction of its voltage sensitivity through the coupling to channel gating. A similar shift in the activation voltage was noted for the effects of n–6 arachidonic acid (AA) and DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time-dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5 channel opening is a prerequisite for the PUFA-channel interaction. Similar to the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply increased in the range of membrane potentials that coincided with the range of Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are also coupled to channel gating. Furthermore, AA regulates the inactivation process in other Kv channels, introducing a fast voltage-dependent inactivation in non-inactivating Kv channels. These results have been explained within the framework that AA closes voltage-dependent potassium channels by inducing conformational changes in the selectivity filter, suggesting that Kv channel gating is lipid dependent. Frontiers Research Foundation 2012-09-10 /pmc/articles/PMC3437463/ /pubmed/22973228 http://dx.doi.org/10.3389/fphar.2012.00163 Text en Copyright © 2012 Moreno, Macias, Prieto, De La Cruz and Valenzuela. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Moreno, Cristina Macias, Alvaro Prieto, Angela De La Cruz, Alicia Valenzuela, Carmen
spellingShingle	Moreno, Cristina Macias, Alvaro Prieto, Angela De La Cruz, Alicia Valenzuela, Carmen Polyunsaturated Fatty Acids Modify the Gating of Kv Channels
author_facet	Moreno, Cristina Macias, Alvaro Prieto, Angela De La Cruz, Alicia Valenzuela, Carmen
author_sort	Moreno, Cristina
title	Polyunsaturated Fatty Acids Modify the Gating of Kv Channels
title_short	Polyunsaturated Fatty Acids Modify the Gating of Kv Channels
title_full	Polyunsaturated Fatty Acids Modify the Gating of Kv Channels
title_fullStr	Polyunsaturated Fatty Acids Modify the Gating of Kv Channels
title_full_unstemmed	Polyunsaturated Fatty Acids Modify the Gating of Kv Channels
title_sort	polyunsaturated fatty acids modify the gating of kv channels
description	Polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which are attributed to their capability to modulate ion channels. This PUFAs ability has been reported to be due to their effects on the gating properties of ion channels. In the present review, we will focus on the role of PUFAs on the gating of two Kv channels, Kv1.5 and Kv11.1. Kv1.5 channels are blocked by n−3 PUFAs of marine [docosahexaenoic acid (DHA) and eicosapentaenoic acid] and plant origin (alpha-linolenic acid, ALA) at physiological concentrations. The blockade of Kv1.5 channels by PUFAs steeply increased in the range of membrane potentials coinciding with those of Kv1.5 channel activation, suggesting that PUFAs-channel binding may derive a significant fraction of its voltage sensitivity through the coupling to channel gating. A similar shift in the activation voltage was noted for the effects of n–6 arachidonic acid (AA) and DHA on Kv1.1, Kv1.2, and Kv11.1 channels. PUFAs-Kv1.5 channel interaction is time-dependent, producing a fast decay of the current upon depolarization. Thus, Kv1.5 channel opening is a prerequisite for the PUFA-channel interaction. Similar to the Kv1.5 channels, the blockade of Kv11.1 channels by AA and DHA steeply increased in the range of membrane potentials that coincided with the range of Kv11.1 channel activation, suggesting that the PUFAs-Kv channel interactions are also coupled to channel gating. Furthermore, AA regulates the inactivation process in other Kv channels, introducing a fast voltage-dependent inactivation in non-inactivating Kv channels. These results have been explained within the framework that AA closes voltage-dependent potassium channels by inducing conformational changes in the selectivity filter, suggesting that Kv channel gating is lipid dependent.
publisher	Frontiers Research Foundation
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3437463/
_version_	1611555321942114304

Polyunsaturated Fatty Acids Modify the Gating of Kv Channels

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