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 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. [(3)H]-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 (< or =1.0) at the concentrations that affect myocyte contraction and the conductance of voltage-dependent Na(+) and L-type Ca(2)+ channels in rat cardiomyocytes and in alpha-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. J. Lipid Res. 2001. 42: 346--351.
Department of Medicine, Massachusetts General Hospital and the Harvard Medical School, Boston, MA 02114, USA.
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Pound
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Kang
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Leaf
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000032:analysis / Q000737:chemistry; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000737:chemistry*; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D004553:Electric Conductivity; D004910:Erythrocyte Membrane / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D008563:Membrane Lipids / Q000737:chemistry*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D010743:Phospholipids / Q000032:analysis / Q000737:chemistry*; D010758:Phosphorus / Q000032:analysis; D051381:Rats; D012508:Sarcolemma / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014316:Tritium
D020746:Calcium Channels, L-Type; D005231:Fatty Acids, Unsaturated; D007473:Ion Channels; D008563:Membrane Lipids; D010743:Phospholipids; D015222:Sodium Channels; D014316:Tritium; D004281:Docosahexaenoic Acids; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D010758:Phosphorus; D015118:Eicosapentaenoic Acid