Incorporated sarcolemmal fish oil fatty acids shorten pig ventricular action potentials.
BACKGROUND
Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil reduce the risk of sudden death presumably by preventing life-threatening arrhythmias. Acutely administered omega3-PUFAs modulate the activity of several cardiac ion channels, but the chronic effects of a diet enriched with fish oil leading to omega3-PUFA-incorporation into the sarcolemma on membrane currents are unknown.


METHODS
Pigs received a diet either rich in omega3-PUFAs or in omega9-fatty acids for 8 weeks. Ventricular myocytes (VMs) were isolated and used for patch-clamp studies.


RESULTS
omega3-VMs contained higher amounts of omega3-PUFAs and had a shorter action potential (AP) with a more negative plateau than control VM. In omega3 VMs, L-type Ca(2+) current (I(Ca,L)) and Na(+)-Ca(2+) exchange current (I(NCX)) were reduced by approximately 20% and 60%, respectively, and inward rectifier K(+) current (I(K1)) and slow delayed rectifier K(+) current (I(Ks)) were increased by approximately 50% and 70%, respectively, compared to control. Densities of rapid delayed rectifier K(+) current, Ca(2+)-activated Cl(-) current, and Na(+) current (I(Na)) were unchanged, although voltage-dependence of I(Na) inactivation was more negative in omega3 VMs.


CONCLUSIONS
A fish oil diet increases omega3-PUFA content in the ventricular sarcolemma, decreases I(Ca,L) and I(NCX), and increases I(K1) and I(Ks), resulting in AP shortening. Incorporation of omega3-PUFAs in the sarcolemma may have consequences for arrhythmias independent of circulating omega3-PUFAs.
Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands.
Arie O
AO
Verkerk
Antoni C G
AC
van Ginneken
Géza
G
Berecki
Hester M
HM
den Ruijter
Cees A
CA
Schumacher
Marieke W
MW
Veldkamp
Antonius
A
Baartscheer
Simona
S
Casini
Tobias
T
Opthof
Robert
R
Hovenier
Jan W T
JW
Fiolet
Peter L
PL
Zock
Ruben
R
Coronel
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils; D006352:Heart Ventricles; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D012508:Sarcolemma / Q000378:metabolism / Q000502:physiology*; D015222:Sodium Channels / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D013552:Swine; D013997:Time Factors
D000975:Antioxidants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002839:Chromans; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; C029141:2,2,5,7,8-pentamethyl-1-hydroxychroman; D009543:Nifedipine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid