Effects of Eicosapentaenoic Acid on the Contraction of Intact, and Spontaneous Contraction of Chemically Permeabilized Mammalian Ventricular Myocytes

The n-3 polyunsaturated fatty acids appear to protect the heart from ischaemia-induced arrhythmias. We have used single adult guinea-pig and rat ventricular myocytes to investigate the effects of the n-3 polyunsaturated fatty acid eicosapentaenoic acid on, (i) the -type Ca2+current, (ii) twitch contraction, and (iii) the spontaneous mechanical activity induced in chemically skinned myocytes by an elevation of the superfusing [Ca2+]. Eicosapentaenoic acid reduced the size of the -type Ca2+current in a dose-dependent manner in myocytes from both species. Inclusion of delipidated bovine serum albumin (BSA) to the Tyrode, which binds eicosapentaenoic acid, completely reversed the inhibition of the Ca2+current in both guinea-pig and rat cells. The effects of eicosapentaenoic acid on contraction were species dependent. In guinea-pig myocytes it produced a reduction in contraction size which was complex, being described by three phases. In rat cells there was an initial increase in the size of contractions, followed by a simple reduction in contraction strength. Delipidated BSA completely reversed these effects in rat cells but only partially restored twitch contraction in guinea-pig cells (60%). In saponin permeabilized cells, the frequency of the spontaneous activity evoked by elevation of [Ca2+] was reduced by micromolar concentrations of eicosapentaenoic acid in cells from both species. The reduction in the amplitude of contractions caused by eicosapentaenoic acid can be explained by an inhibition of the -type Ca2+current, and by a reduction in Ca2+released from the sarcoplasmic reticulum (SR). The inhibition of the release of Ca2+from the SR reduces the frequency of [Ca2+] dependent spontaneous contractions in chemically skinned guinea-pig and rat ventricular myocytes.