PROTECTIVE EFFECTS OF FREE POLYUNSATURATED FATTY-ACIDS ON ARRHYTHMIASINDUCED BY LYSOPHOSPHATIDYLCHOLINE OR PALMITOYLCARNITINE IN NEONATAL RAT CARDIAC MYOCYTES
Jx. Kang et A. Leaf, PROTECTIVE EFFECTS OF FREE POLYUNSATURATED FATTY-ACIDS ON ARRHYTHMIASINDUCED BY LYSOPHOSPHATIDYLCHOLINE OR PALMITOYLCARNITINE IN NEONATAL RAT CARDIAC MYOCYTES, European journal of pharmacology, 297(1-2), 1996, pp. 97-106
Cultured, spontaneously beating, neonatal rat cardiac myocytes were us
ed to examine the effects of various free fatty acids added to the med
ium perfusing the cells on lysophosphatidylcholine (LPC)- or acylcarni
tine-induced arrhythmias. Perfusion of the cells with LPC or palmitoyl
carnitine (2-10 mu M) induced sustained tachyrhythmia with episodes of
spasmodic contractures and fibrillation. Free PUFA (10-15 mu M) inclu
ding eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA,
22:6n-3), mu-linolenic acid (18:3n-3), arachidonic acid (AA, 20:4n-6)
and linoleic acid (18:2n-6) were able to effectively prevent as well a
s terminate the LPC or acylcarnitine-induced arrhythmias. In contrast,
monounsaturated oleic acid (18:1n-9) and saturated stearic acid (18:0
) did not have such effects. The protective effects of the polyunsatur
ated fatty acids (PUFA) could be reversed by cell perfusion with delip
idated bovine serum albumin. To determine the potential primary action
by which the PUFA exert the antiarrhythmic effects, measurements of i
ntracellular Ca2+ levels and the response of the cells to electrical p
acing in the absence or presence of the PUFA were performed and the ef
fects of verapamil (a L-type Ca2+ channel blocker), tetrodotoxin (a Na
+ channel blocker) and Ca2+ ionophore A23187 on the cell contraction a
nd the cytosolic Ca2+ levels were compared with that of the PUFA. Resu
lts suggest that an inhibitory effect on the electrical automaticity/e
xcitability of the cardiac myocyte rather than a reduction in cytosoli
c Ca2+ underlie the protective effects of PUFA. In conclusion, free PU
FAs are able to effectively protect the cardiac myocytes against the a
rrhythmias induced by low concentrations of lysophosphatidylcholine or
palmitoylcarnitine.