Inhibitory effect of n-3 fish oil fatty acids on cardiac Na+/Ca2+ exchange currents in HEK293t cells.
Abnormal activity of the cardiac Na+/Ca2+ exchanger (NCX1) can affect intracellular Ca2+ homeostasis and cause arrhythmias. The n-3 polyunsaturated fatty acids (PUFAs), however, may prevent arrhythmias. To test the effect of PUFAs on the cardiac NCX1 current (I(NCX1)), the canine NCX1 cDNA was expressed in human embryonic kidney (HEK293t) cells. The average density of I(NCX1) was 10.9+/-2.6 pA/pF (n=44) in NCX1-transfected cells and eicosapentaenoic acid (EPA, C20:5n-3) significantly inhibited I(NCX1) The suppression of I(NCX1) by EPA was concentration-dependent with an IC50 of 0.82+/-0.27 microM. EPA had a similar effect on outward or inward I(NCX1). Docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, C20:4n-6) also significantly inhibited I(NCX1), whereas the saturated fatty acid, stearic acid (SA, C18:0), did not. Our data demonstrate that the n-3 PUFAs significantly suppress cardiac I(NCX1), which is probably one of their protective effects against lethal arrhythmias.
Xiao
Yong-Fu
YF
Harvard Medical School, Boston, MA 02215, USA.
Ke
Qingen
Q
Chen
Yu
Y
Morgan
James P
JP
Leaf
Alexander
A
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D014162:Transfection
D018076:DNA, Complementary; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D011994:Recombinant Proteins; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1