Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes

It has been demonstrated in animal studies that polyunsaturated fatty acids (PUFA) prevent ischemia-induced malignant ventricular arrhythmias, a major cause of sudden cardiac death in humans. To learn how these PUFA, at low micromolar concentrations, exert their antiarrhythmic activity, we studied t...

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Main Authors: Eric M. Pound, Jing X. Kang, A. Leaf
Format: Article
Language:English
Published: Elsevier 2001-03-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520316576
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spelling doaj-bda2195221aa4ff69cd229841f5afbd92021-04-27T04:40:29ZengElsevierJournal of Lipid Research0022-22752001-03-01423346351Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranesEric M. Pound0Jing X. Kang1A. Leaf2Departments of Medicine, Massachusetts General Hospital, and the Harvard Medical School, Boston, MA 02114Departments of Medicine, Massachusetts General Hospital, and the Harvard Medical School, Boston, MA 02114Massachussetts General Hospital–East Bldg. 149, Room 4001, 13th St. Charlestown MA 02129; Departments of Medicine, Massachusetts General Hospital, and the Harvard Medical School, Boston, MA 02114It has been demonstrated in animal studies that polyunsaturated fatty acids (PUFA) prevent ischemia-induced malignant ventricular arrhythmias, a major cause of sudden cardiac death in humans. To learn how these PUFA, at low micromolar concentrations, exert their antiarrhythmic activity, we studied their effects in vitro on the contractions of isolated cardiac myocytes and the conductances of their sarcolemmal ion channels. These fatty acids directly stabilize electrically every cardiac myocyte by modulating the conductances of specific ion channels in their sarcolemma. In this study, we determined the molar ratio of PUFA to the moles of phospholipid (PL) in cell membranes to learn if the ratio is so low as to preclude the possibility that the primary site of action of PUFA is on the packing of the membrane PL. [3H]-arachidonic acid (AA) was used to measure the incorporation of PUFA, and the inorganic phosphorous of the PL was determined as a measure of the moles of PL in the cell membrane. Our results indicate that the mole percent of AA to moles of phospolipid is very low (≤1.0) at the concentrations that affect myocyte contraction and the conductance of voltage-dependent Na+ and L-type Ca2+ channels in rat cardiomyocytes and in α-subunits of human myocardial Na+ channels. In conclusion, it seems highly unlikely that these fatty acids are affecting the packing of PL within cell membranes as their way of modulating changes in cell membrane ion currents and in preventing arrhythmias in our contractility studies. —Pound, E. M., J. X. Kang, and A. Leaf. Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes.http://www.sciencedirect.com/science/article/pii/S0022227520316576eicosapentaenoic aciddocosahexaenoic acidarachidonic acidfish oilsudden cardiac death
collection DOAJ
language English
format Article
sources DOAJ
author Eric M. Pound
Jing X. Kang
A. Leaf
spellingShingle Eric M. Pound
Jing X. Kang
A. Leaf
Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
Journal of Lipid Research
eicosapentaenoic acid
docosahexaenoic acid
arachidonic acid
fish oil
sudden cardiac death
author_facet Eric M. Pound
Jing X. Kang
A. Leaf
author_sort Eric M. Pound
title Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
title_short Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
title_full Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
title_fullStr Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
title_full_unstemmed Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
title_sort partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes
publisher Elsevier
series Journal of Lipid Research
issn 0022-2275
publishDate 2001-03-01
description It has been demonstrated in animal studies that polyunsaturated fatty acids (PUFA) prevent ischemia-induced malignant ventricular arrhythmias, a major cause of sudden cardiac death in humans. To learn how these PUFA, at low micromolar concentrations, exert their antiarrhythmic activity, we studied their effects in vitro on the contractions of isolated cardiac myocytes and the conductances of their sarcolemmal ion channels. These fatty acids directly stabilize electrically every cardiac myocyte by modulating the conductances of specific ion channels in their sarcolemma. In this study, we determined the molar ratio of PUFA to the moles of phospholipid (PL) in cell membranes to learn if the ratio is so low as to preclude the possibility that the primary site of action of PUFA is on the packing of the membrane PL. [3H]-arachidonic acid (AA) was used to measure the incorporation of PUFA, and the inorganic phosphorous of the PL was determined as a measure of the moles of PL in the cell membrane. Our results indicate that the mole percent of AA to moles of phospolipid is very low (≤1.0) at the concentrations that affect myocyte contraction and the conductance of voltage-dependent Na+ and L-type Ca2+ channels in rat cardiomyocytes and in α-subunits of human myocardial Na+ channels. In conclusion, it seems highly unlikely that these fatty acids are affecting the packing of PL within cell membranes as their way of modulating changes in cell membrane ion currents and in preventing arrhythmias in our contractility studies. —Pound, E. M., J. X. Kang, and A. Leaf. Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes.
topic eicosapentaenoic acid
docosahexaenoic acid
arachidonic acid
fish oil
sudden cardiac death
url http://www.sciencedirect.com/science/article/pii/S0022227520316576
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