Dietary fish oil reduces pacemaker current and heart rate in rabbit

Abstract

Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil (FO) reduce heart rate in humans. The mechanism underlying this cardioprotective effect of FO is unknown. We studied the effects of an FO diet on heart rate, pacemaker activity, and pacemaker current (I(f)) in sinoatrial node (SAN) cells. Rabbits were fed a diet enriched with 2.5% (w/w) FO or 2.5% high oleic sunflower oil (SO) as control for 3 weeks. Heart rate was measured in Langendorff-perfused hearts. Pacemaker activity and I(f) were recorded using the perforated patch-clamp technique in isolated SAN cells. In SAN cells, the FO diet reduced I(f) density by approximately 30%, without changes in its voltage dependence, reversal potential, (de)activation kinetics, and sensitivity to beta-stimulation. Dietary FO significantly prolonged the cycle length in both isolated perfused hearts (337 +/- 8 [mean +/- SEM, n = 8] vs. 301 +/- 9 ms [n = 8]) and single cells (363 +/- 20 [n = 19] vs. 276 +/- 8 ms [n = 22]). In single cells, dietary FO significantly decreased the diastolic depolarization rate by 33% and prolonged the action potential by 27%, whereas other action potential parameters were unaltered. I(f) blockade experiments substantiated that the reduced diastolic depolarization rate in the FO group was partially caused by the I(f) density reduction. An FO diet prolongs the sinus cycle length because of, at least in part, a reduction in I(f) density. Our results explain FO-induced heart rate reduction and suggest FO as an alternative or adjunct to I(f)-lowering drugs.