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Title

Modulation of the atrial specific Kv1.5 channel by the n-3 polyunsaturated fatty acid, α-linolenic acid

AuthorsGuizy, Miriam ; David, Miren ; Arias, Cristina; Zhang, Lian; Cofán, Montserrat; Ruiz-Gutiérrez, Valentina ; Ros, Emilio; Lillo, M. Pilar ; Martens, Jeffrey R.; Valenzuela, Carmen
KeywordsKv1.5 Potassium channel
Alpha-Linolenic acid
Heart atria
Membrane fluidity
Issue DateFeb-2008
PublisherElsevier
CitationJournal of Molecular and Cellular Cardiology 44(2): 323-335 (2008)
AbstractEpidemiological, clinical and experimental studies suggest that the cardioprotective effect of fish intake is mainly due to the antiarrhythmic properties of marine n-3 polyunsaturated fatty acids (PUFA), which modulate ion currents. Emerging evidences point to similar effects of alpha-linolenic acid (ALA), a vegetable n-3 PUFA, but much less is known about its effects on the specific cardiac ion channels. Using electrophysiology, protein biochemistry and fluorescence anisotropy measurements, we tested the effects of ALA on the atrial specific Kv1.5 channel. In stably transfected Ltk(-) cells, ALA blocked Kv1.5 channels in a time- and voltage-dependent manner with an IC(50) value of 3.7+/-0.3 microM. ALA at 2.5 microM inhibited the Kv1.5 current, shifted the midpoint of the activation curve by -8.8+/-4.3 mV (p<0.05), accelerated the activation kinetics of Kv1.5 due to a negative shift in its voltage dependency and slowed its deactivation process. Marine n-3 PUFA eicosapentaenoic and docosahexaenoic (EPA and DHA) acids, but not ALA, reduced the steady-state levels of Kv1.5 protein. DHA, but not ALA, increased the cell membrane order parameter. These results demonstrate that ALA directly blocks atria-specific Kv1.5 channels without modifying their expression or the bilayer order. Together, these effects suggest that the antiarrhythmic potential of diets enriched with plant-derived n-3 PUFA result, in part, from direct effects on cardiac ion channels.
Publisher version (URL)http://dx.doi.org/10.1016/j.yjmcc.2007.11.004
URIhttp://hdl.handle.net/10261/55540
DOI10.1016/j.yjmcc.2007.11.004
ISSN0022-2828
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