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In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K + Channels; Interaction and New Targets

View Article: PubMed Central - PubMed

ABSTRACT

Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation.

No MeSH data available.


Chemical structures of representative fatty acids (monounsaturated: n-9 MUFA, n-3, and n-6 PUFAs) and modified PUFAs (DHA-ethyl-ester DHA and DHA-amine: non-charged and permanently charged, respectively).
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Figure 1: Chemical structures of representative fatty acids (monounsaturated: n-9 MUFA, n-3, and n-6 PUFAs) and modified PUFAs (DHA-ethyl-ester DHA and DHA-amine: non-charged and permanently charged, respectively).

Mentions: It has been reported that an increased consumption of omega 3 polyunsaturated fatty acids (n-3 PUFAs; Figure 1) have beneficial properties for the cardiovascular system (Chaddha and Eagle, 2015) and neurological diseases such as epilepsy and pain (Lefevre and Aronson, 2000). Among other targets, the beneficial actions of n-3 PUFAs occur through the modulation of a big variety of K+ voltage gated ion channels (Boland and Drzewiecki, 2008; Moreno et al., 2012). For instance, it is known that n-3 PUFAs activate different members of the KV7 channel family. In the heart, n-3 PUFA dependent activation of KV7.1 channels (pore forming component of the cardiac IKs) reduces the risk of arrhythmia by shortening the action potential duration (Verkerk et al., 2006; Liin et al., 2015; Moreno et al., 2015). In the neuronal system, the activation of KV7.2/KV7.3 channels (major components of the neuronal M-current) decreases neuronal excitability and therefore the risk of seizure (Liin et al., 2016; Valenzuela, 2016).


In-Depth Study of the Interaction, Sensitivity, and Gating Modulation by PUFAs on K + Channels; Interaction and New Targets
Chemical structures of representative fatty acids (monounsaturated: n-9 MUFA, n-3, and n-6 PUFAs) and modified PUFAs (DHA-ethyl-ester DHA and DHA-amine: non-charged and permanently charged, respectively).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121229&req=5

Figure 1: Chemical structures of representative fatty acids (monounsaturated: n-9 MUFA, n-3, and n-6 PUFAs) and modified PUFAs (DHA-ethyl-ester DHA and DHA-amine: non-charged and permanently charged, respectively).
Mentions: It has been reported that an increased consumption of omega 3 polyunsaturated fatty acids (n-3 PUFAs; Figure 1) have beneficial properties for the cardiovascular system (Chaddha and Eagle, 2015) and neurological diseases such as epilepsy and pain (Lefevre and Aronson, 2000). Among other targets, the beneficial actions of n-3 PUFAs occur through the modulation of a big variety of K+ voltage gated ion channels (Boland and Drzewiecki, 2008; Moreno et al., 2012). For instance, it is known that n-3 PUFAs activate different members of the KV7 channel family. In the heart, n-3 PUFA dependent activation of KV7.1 channels (pore forming component of the cardiac IKs) reduces the risk of arrhythmia by shortening the action potential duration (Verkerk et al., 2006; Liin et al., 2015; Moreno et al., 2015). In the neuronal system, the activation of KV7.2/KV7.3 channels (major components of the neuronal M-current) decreases neuronal excitability and therefore the risk of seizure (Liin et al., 2016; Valenzuela, 2016).

View Article: PubMed Central - PubMed

ABSTRACT

Voltage gated potassium channels (KV) are membrane proteins that allow selective flow of K+ ions in a voltage-dependent manner. These channels play an important role in several excitable cells as neurons, cardiomyocytes, and vascular smooth muscle. Over the last 20 years, it has been shown that omega-3 polyunsaturated fatty acids (PUFAs) enhance or decrease the activity of several cardiac KV channels. PUFAs-dependent modulation of potassium ion channels has been reported to be cardioprotective. However, the precise cellular mechanism underlying the cardiovascular benefits remained unclear in part because new PUFAs targets and signaling pathways continue being discovered. In this review, we will focus on recent data available concerning the following aspects of the KV channel modulation by PUFAs: (i) the exact residues involved in PUFAs-KV channels interaction; (ii) the structural PUFAs determinants important for their effects on KV channels; (iii) the mechanism of the gating modulation of KV channels and, finally, (iv) the PUFAs modulation of a few new targets present in smooth muscle cells (SMC), KCa1.1, K2P, and KATP channels, involved in vascular relaxation.

No MeSH data available.