Verkerk Arie O, van Ginneken Antoni C G, Berecki Géza, den Ruijter Hester M, Schumacher Cees A, Veldkamp Marieke W, Baartscheer Antonius, Casini Simona, Opthof Tobias, Hovenier Robert, Fiolet Jan W T, Zock Peter L, Coronel Ruben
Experimental and Molecular Cardiology Group, Academic Medical Center, University of Amsterdam, The Netherlands.
Cardiovasc Res. 2006 Jun 1;70(3):509-20. doi: 10.1016/j.cardiores.2006.02.022. Epub 2006 Feb 28.
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.
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.
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.
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.
鱼油中的ω-3多不饱和脂肪酸(ω3-PUFA)可能通过预防危及生命的心律失常来降低猝死风险。急性给予ω3-PUFA可调节多种心脏离子通道的活性,但富含鱼油的饮食导致ω3-PUFA掺入肌膜对膜电流的长期影响尚不清楚。
猪接受富含ω3-PUFA或ω9-脂肪酸的饮食8周。分离心室肌细胞(VM)并用于膜片钳研究。
ω3-VM含有更高含量的ω3-PUFA,其动作电位(AP)较短,平台期更负,比对照VM短。在ω3-VM中,L型Ca(2+)电流(I(Ca,L))和Na(+)-Ca(2+)交换电流(I(NCX))分别降低约20%和60%,内向整流K(+)电流(I(K1))和缓慢延迟整流K(+)电流(I(Ks))分别增加约50%和70%,与对照相比。快速延迟整流K(+)电流、Ca(2+)-激活Cl(-)电流和Na(+)电流(I(Na))的密度未改变,尽管ω3-VM中I(Na)失活的电压依赖性更负。
鱼油饮食增加心室肌膜中ω3-PUFA的含量,降低I(Ca,L)和I(NCX),增加I(K1)和I(Ks),导致AP缩短。肌膜中ω3-PUFA的掺入可能对心律失常产生影响,独立于循环中的ω3-PUFA。