During myocardial ischaemia free fatty acids accumulate in the ischaemic tissue, released by phospholipase A2 (Ford et al. 1991). The n-3 class of polyunsaturated fatty acids (PUFAs) are known to have anti-arrhythmic properties at least part of which is due to direct inhibitory effects on the Ca²⁺ release mechanism of the sarcoplasmic reticulum (SR) and a consequent reduction in the frequency of arrhythmogenic waves of Ca²⁺-induced Ca²⁺ release (CICR; O’Neill et al. 2002). However, n-3 PUFAs can only be released if they have been previously present in the diet. In their absence the n-6 PUFAs are released in greater amounts. The anti-arrhythmic properties of n-6 PUFAs are much less clear than those of the n-3 class of fatty acid. Some reports have shown inhibition of delayed after-depolarizations but the mechanism is not yet known (Mamas & Terrar, 2001). We have used the n-6 PUFA arachidonic acid to determine if there is an effect on arrhythmogenic waves of CICR and, if so, where it is exerted.

In voltage clamp experiments using the perforated patch, we have measured transient inward currents activated by propagation of waves of CICR in Ca²⁺ overloaded rat ventricular myocytes isolated following humane killing. The frequency of these waves is lower in the presence of 50 µM arachidonic acid. Much previous work has shown that changes in wave frequency brought about by modulation of the sensitivity of the Ca²⁺ release mechanism are associated with changes in SR Ca²⁺ content (e.g. Overend et al. 1997). In the presence of arachidonic acid, SR Ca²⁺ content rises by 12.3 ± 4.0 % (mean ± S.E.M., n = 5; P < 0.03 Student’s paired t test). Although this increase is statistically significant, it is moderate in size. The n-3 class of PUFA can increase SR content by 50 % at lower concentrations than those used here for arachidonic acid.

We conclude that n-6 PUFAs have two effects that reduce the frequency of waves of CICR: a weak inhibitory effect on the ryanodine receptor and, more importantly, a reduction of Ca²⁺ influx. These two mechanisms are also involved when n-3 PUFAs reduce the frequency of waves of Ca²⁺ release but the majority of the effect is due to inhibition of CICR (O’Neill et al. 2002).