2014
DOI: 10.1093/cvr/cvu250
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Marine n-3 PUFAs modulate IKs gating, channel expression, and location in membrane microdomains

Abstract: We provide evidence that acute application of PUFAs increases Kv7.1/KCNE1 through a probably direct effect, and shows antiarrhythmic efficacy under IKr block. Conversely, chronic EPA application modifies the channel activity through a change in the Kv7.1/KCNE1 voltage-dependence, correlated with a redistribution of Kv7.1 over the cell membrane. This loss of function may be pro-arrhythmic. This shed light on the controversial effects of PUFAs regarding arrhythmias.

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Cited by 26 publications
(55 citation statements)
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References 43 publications
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“…2E), consistent with previous studies (20,23,32), the Boltzmann fits obtained here may have been biased toward the hyperpolarized direction. Furthermore, because the g max values reported here were the results of extrapolation, they should be interpreted with caution.…”
Section: Discussionsupporting
confidence: 92%
“…2E), consistent with previous studies (20,23,32), the Boltzmann fits obtained here may have been biased toward the hyperpolarized direction. Furthermore, because the g max values reported here were the results of extrapolation, they should be interpreted with caution.…”
Section: Discussionsupporting
confidence: 92%
“…This finding suggests that PUFAs and fish oil do not act antiarrhythmically by altering the voltage dependence of the Kv7.1/KCNE1 channel. Recently, Moreno et al found that acute DHA and EPA applications increased the Kv7.1/KCNE1 currents and that acute EPA application shifted the Kv7./KCNE1 activation moderately to more hyperpolarized voltages (49). However, chronic applications of DHA and EPA did not increase the currents, and EPA even shifted the activation moderately to more depolarized voltages.…”
Section: Discussionmentioning
confidence: 98%
“…However, chronic applications of DHA and EPA did not increase the currents, and EPA even shifted the activation moderately to more depolarized voltages. Chronic EPA and DHA application also redistributed the Kv7.1 subunits and decreased their expression levels (49). The complex results from Moreno et al suggest that more studies are necessary to clarify the clinical relevance of the effects of PUFAs on I Ks channels.…”
Section: Discussionmentioning
confidence: 99%
“…The poor DHA sensitivity of the hK V 7.1/hKCNE1 complex under similar conditions is likely caused by KCNE1-induced protonation of DHA (Liin et al 2015a). Future work that compares the detailed PUFA binding sites in these channels is required for a molecular understanding of differential PUFA sensitivity and differential impact of KCNE co-expression on PUFA sensitivity in K V channels (Liin et al 2015a;Moreno et al 2015).…”
Section: Discussionmentioning
confidence: 99%
“…It remains however to be determined whether the K V 7.2/3 channel and KCNE subunits form functional neuronal complexes in vivo. PUFA effects on the hK V 7.1 channel are altered by KCNE co-expression (Liin et al 2015a;Moreno et al 2015). We therefore tested whether KCNE co-expression altered PUFA effects on the hK V 7.2/3 channel.…”
Section: Kcne Co-expression Does Not Alter Dha Sensitivity Of the Hk mentioning
confidence: 99%