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 ischae mia-induced arrhythmias. We have used single adult guinea-pig and rat ventr icular myocytes to investigate the effects of the n-3 polyunsaturated fatty acid eicosapentaenoic acid on, (i) the L-type Ca2+ current, (ii) twitch co ntraction, and (iii) the spontaneous mechanical activity induced in chemica lly skinned myocytes by an elevation of the superfusing [Ca2+]. Eicosapenta enoic acid reduced the size of the L-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 cel ls, The effects of eicosapentaenoic acid on contraction were species depend ent. In guinea-pig myocytes ii. produced a reduction in contraction size wh ich was complex, being described by three phases. In rat cells there was an initial increase in the size of contractions, followed by a simple reducti on in contraction strength, Delipidated BSA completely reversed these effec ts in rat cells but only partially restored twitch contraction in guinea-pi g cells (60%), In saponin permeabilized cells, the frequency of the spontan eous activity evoked by elevation of [Ca2+] was reduced by micromolar conce ntrations of eicosapentaenoic acid in cells from both species. The reductio n in the amplitude of contractions caused by eicosapentaenoic acid can be e xplained by an inhibition of the L-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 spont aneous contractions in chemically skinned guinea-pig and rat ventricular my ocytes, (C) 1999 Academic Press.