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Title

ω-3 and ω-6 polyunsaturated fatty acids block HERG channels

AuthorsGuizy, Miriam CSIC; Arias, Cristina; David, Miren CSIC; González, Teresa; Valenzuela, Carmen CSIC ORCID CVN
KeywordsK+ channel
Membrane currents
Ion channels
Arrhythmias
Antiarrhythmics
Issue DateNov-2005
PublisherAmerican Physical Society
CitationAmerican Journal of Physiology - Cell Physiology 289(5): C1251-C1260 (2005)
AbstractDietary polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, which have been attributed to their availability to modulate Na(+), Ca(2+), and several K(+) channels. However, their effects on human ether-a-go-go-related gene (HERG) channels are unknown. In this study we have analyzed the effects of arachidonic acid (AA, omega-6) and docosahexaenoic acid (DHA, omega-3) on HERG channels stably expressed in Chinese hamster ovary cells by using the whole cell patch-clamp technique. At 10 microM, AA and DHA blocked HERG channels, at the end of 5-s pulses to -10 mV, to a similar extent (37.7 +/- 2.4% vs. 50.2 +/- 8.1%, n = 7-10, P > 0.05). 5,6,11,14-Eicosatetrayenoic acid, a nonmetabolizable AA analog, induced effects similar to those of AA on HERG current. Both PUFAs shifted the midpoint of activation curves of HERG channels by -5.1 +/- 1.8 mV (n = 10, P < 0.05) and -11.2 +/- 1.1 mV (n = 7, P < 0.01). Also, AA and DHA shifted the midpoint of inactivation curves by +12.0 +/- 3.9 mV (n = 4; P < 0.05) and +15.8 +/- 4.3 mV (n = 4; P < 0.05), respectively. DHA and AA accelerated the deactivation kinetics and slowed the inactivation kinetics at potentials positive to +40 mV. Block induced by DHA, but not that produced by AA, was higher when measured after applying a pulse to -120 mV (I-->O). Finally, both AA and DHA induced a use-dependent inhibition of HERG channels. In summary, block induced by AA and DHA was time, voltage, and use dependent. The results obtained suggest that both PUFAs bind preferentially to the open state of the channel, although an interaction with inactivated HERG channels cannot be ruled out for AA.
Description11 pages, 7 figures.
Publisher version (URL)http://dx.doi.org/10.1152/ajpcell.00036.2005
URIhttp://hdl.handle.net/10261/24654
DOI10.1152/ajpcell.00036.2005
ISSN0363-6143
Appears in Collections:(IFTOX) Artículos
(IIBM) Artículos




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