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Effects of polyunsaturated fatty acids on cardiac voltage-activated K+ currents in adult ferret cardiomyocytes

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Author:: No author available

Journal Title:: ACTA PHYSIOLOGICA SINICA

Issue:: 4

DOI:: 10.3321/j.issn:0371-0874.2002.04.001

Key Word:: 心肌细胞;钾通道;心律失常;多不饱和脂肪酸;cardiomyocytes;potassium channels;arrhythmia;polyunsaturated fatty acids

Abstract： This study was carried out in adult ferret cardiomyocytes to investigate the effects of the n-3 polyunsaturated fatty acids (PUFAs) on voltage-gated K+ currents. We report that the two outward K+ currents: the transient outward K+ current (Ito) and the delayed rectifier K+ current (IK), are both inhibited by the n-3 PUFAs, while the inwardly rectifying K+ current (IK1) is unaffected by the n-3 PUFAs. Docosahexaenoic acid (C22:6n-3, DHA) produced a concentration-dependent suppression of Ito and IK in adult ferret cardiomyocytes with an IC50 of 7.5 and 20 μmol/L, respectively; but not IK1. In addition, eicosapentaenoic acid (C20:5n-3, EPA) had the effects on the three K+ channels similar to DHA. Arachidonic acid (C20:4n-6, AA) at 5 or 10 μmol/L, after an initial inhibitory effect on IK, caused an activation of IK,AA which was prevented by pretreatment with indomethacin, a cyclooxygenase inhibitor. Monounsaturated and saturated fatty acids, which are not antiarrhythmic, lack the effects on these K+ currents. Our results demonstrate that the n-3 PUFAs inhibit cardiac Ito and IK with much less potency compared to their effects on cardiac Na+ and Ca2+ currents as we reported previously. This inhibition of the cardiac ion currents by the n-3 PUFAs may contribute to their antiarrhythmic actions.

Reference

[1]WA Catterall.Structure and function of voltage-sensitive ion channels[J].1988,242 (4875).
[2]Yong-Fu Xiao,Joseph McArdle.Elevated density and altered pharmacologic properties of myocardial calcium current of the spontaneously hypertensive rat[J].1994,12(7).
[3]H, Hallaq,T W, Smith,A, Leaf.Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish oil fatty acids.[J].1992,89.
[4]M de Lorgeril,S Renaud,P Salen,etc.Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease[J].1994,343(8911).
[5]J X, Kang,A, Leaf.Effects of long-chain polyunsaturated fatty acids on the contraction of neonatal rat cardiac myocytes.[J].1994,91.
[6]McLennan P. L.,Abeywardena M. Y.,Charnock J. S..Influence of dietary lipids on arrhythmias and infarction after coronary artery ligation in rats[J].1985.
[7]Wright SN,Morgan JP,Wang GK,etc.Fatty acids suppress voltage-gated Na+ currents in HEK293t cells transfected with the alpha-subunit of the human cardiac Na+ channel.[J].1998,95(5).
[8]Gomez AM.,Lederer WJ.,Morgan JP.,etc.Suppression of Voltage-Gated L-Type Ca2+ Currents by Polyunsaturated Fatty Acids in Adult and Neonatal Rat Ventricular Myocytes[J].1997,94(8).
[9]J J, Pancrazio,M J, Frazer,C, Lynch.Barbiturate anesthetics depress the resting K+ conductance of myocardium.[J].1993,265(1).
[10]O.P.Hamill,A.Marty,E.Neher,etc.Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches[J].1981,391(2).
[11]G E, Billman,J X, Kang,A, Leaf.Prevention of sudden cardiac death by dietary pure omega-3 polyunsaturated fatty acids in dogs.[J].1999,99.
[12]J S, Poling,J W, Karanian,N, Salem,etc.Time- and voltage-dependent block of delayed rectifier potassium channels by docosahexaenoic acid.[J].1995,47.
[13]NOMA Akinori,NAKAYAMA Toshio,KURACHI Yoshihisa,etc.Resting K conductances in pacemaker and non-pacemaker heart cells of the rabbit.[J].1984.
[14]Noritsugu Tohse,Masaki Kameyama,Kazuo Sekiguchi,etc.Protein kinase C activation enhances the delayed rectifier potassium current in guinea-pig heart cells[J].1990,22(6).
[15]Chung S,Jung W,Lee MY.Inward and outward rectifying potassium currents set membrane potentials in activated rat microglia.[J].1999,262(2).
[16]Linden D J,Routtenberg A.cis-Fatty acids, which activate protein kinase C, attenuate Na+ and Ca2+ currents in mouse neuroblastoma cells.[J].1989,419(1).
[17]Burr, M.L.,Fehily, A.M..Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfraction: Diet and..[J].1989,334(8666).
[18]Kang JX,Leaf A,Xiao YF.Free, long-chain, polyunsaturated fatty acids reduce membrane electrical excitability in neonatal rat cardiac myocytes.[J].1995,92(9).
[19]Jing X. Kang,Alexander Leaf.Evidence that free polyunsaturated fatty acids modify Na~+ channels by directly binding to the channel proteins[J].1996,93(8).
[20]P L, McLennan,T M, Bridle,M Y, Abeywardena,etc.Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey.[J].1992,123(6).
[21]E, Honoré,J, Barhanin,B, Attali,etc.External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids.[J].1994,91.
[22]Morgan JP.,Leaf A.,Kang JX.,etc.Blocking Effects of Polyunsaturated Fatty Acids on Na+ Channels of Neonatal Rat Ventricular Myocytes[J].1995,92(24).
[23]KANIGULA MUBAGWA,WILLEM FLAMENG,EDWARD CARMELIET.Resting and Action Potentials of Nonischemic and Chronically Ischemic Human Ventricular Muscle[J].1994,5(8).
[24]Vinogradova TM,Lakatta EG,Bogdanov KY,etc.Modulation of the transient outward current in adult rat ventricular myocytes by polyunsaturated fatty acids.[J].1998,274(2 Pt.2).
[25]J X, Kang,A, Leaf.Protective effects of All-trans-retinoic acid against cardiac arrhythmias induced by isoproterenol, lysophosphatidylcholine or ischemia and reperfusion.[J].1995,26.