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 m icromolar concentrations, exert their antiarrhythmic activity, we studied t heir effects in vitro on the contractions of isolated cardiac myocytes and the conductances of their sarcolemmal ion channels, These fatty acids direc tly stabilize electrically every cardiac myocyte by modulating the conducta nces of specific ion channels in their sarcolemma, In this study, we determ ined the molar ratio of PUFA to the moles of phospholipid (PL) in cell memb ranes to learn if the ratio is so lo rv as to preclude the possibility that the primary site of action of PUFA is on the packing of the membrane FL. [ H-3]-arachidonic acid (AA) was used to measure the incorporation of PUFA, a nd the inorganic phosphorous of the PL was determined as a measure of the m oles of PL in the cell membrane. Our results indicate that the mole percent of AA to moles of phospolipid is very low (less than or equal to1.0) at th e concentrations that affect myocyte contraction and the conductance of vol tage-dependent Na+ and L-type Ca2+ channels in rat cardiomyocytes and in al pha -subunits of human myocardial Na+ channels. In conclusion, it seems hig hly unlikely that these fatty acids are affecting the packing of PL within cell membranes as their way of modulating changes in cell membrane ion curr ents and in preventing arrhythmias in our contractility studies.