title: Dietary fish oil reduces pacemaker current and heart rate in rabbit.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  We studied the effects of an FO diet on heart rate, pacemaker activity, and pacemaker current (I(f)) in sinoatrial node (SAN) cells.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. A.O.Verkerk@amc.uva.nl
authors.forename: Arie O
authors.initials: AO
authors.lastname: Verkerk
authors.forename: Hester M
authors.initials: HM
authors.lastname: den Ruijter
authors.forename: Jan
authors.initials: J
authors.lastname: Bourier
authors.forename: Bastiaan J
authors.initials: BJ
authors.lastname: Boukens
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Brouwer
authors.forename: Ronald
authors.initials: R
authors.lastname: Wilders
authors.forename: Ruben
authors.initials: R
authors.lastname: Coronel
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006368:Helianthus; D066298:In Vitro Techniques; D008297:Male; D019301:Oleic Acid / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects
chemical_list: D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D019301:Oleic Acid