Macleod J C, Macknight A D, Rodrigo G C
Department of Physiology, Otago Medical School, University of Otago, Dunedin, New Zealand.
Eur J Pharmacol. 1998 Sep 4;356(2-3):261-70. doi: 10.1016/s0014-2999(98)00528-7.
Single adult guinea-pig and rat ventricular cardiac myocytes were used to study the effects of two members of the omega3 class of polyunsaturated fatty acids, docosahexaenoic acid and eicosapentaenoic acid, on the electrical and mechanical activity of cardiac muscle. Docosahexaenoic acid and eicosapentaenoic acid reduced the electrical excitability of both guinea-pig and rat cells in a dose-dependent manner. Both agents produced a dose-dependent negative inotropic response in guinea-pig cells but in the rat cells there was first a dose-dependent positive inotropic effect at low concentrations (< 10 microM) followed by a negative inotropic effect at higher concentrations (> 10 microM). Possible mechanisms by which these agents affect contraction were studied using conventional electrophysiological techniques. The polyunsaturated fatty acids reduced the action potential duration and the plateau potential of the guinea-pig cells in a simple, dose-dependent manner. In contrast, the effect on the rat action potential mirrored the inotropic effect. At low concentrations (< 10 microM) there was a concentration-dependent increase in action potential duration followed by a concentration-dependent decrease at higher concentrations (> 10 microM). Both polyunsaturated fatty acids decreased the fast Na+ current and the L-type Ca2+ current in a concentration-dependent but not use-dependent manner in cells from both species. In the rat cells these agents inhibited the transient outward current resulting in an increase in the duration of the rat action potential. The effects of polyunsaturated fatty acids on the Ca2+, Na+ and K+ currents underlie these changes in the action potentials in guinea-pig and rat heart cells. The effects on the L-type Ca2+ current and action potential duration can also explain both the simple negative inotropic effects of the agents on the guinea-pig cells and the more complex effects on the rat cells. These effects of polyunsaturated fatty acids on membrane currents may account for their anti-arrhythmic properties.
采用成年豚鼠和大鼠的单个心室心肌细胞，研究多不饱和脂肪酸ω-3类的两个成员二十二碳六烯酸和二十碳五烯酸对心肌电活动和机械活动的影响。二十二碳六烯酸和二十碳五烯酸以剂量依赖的方式降低了豚鼠和大鼠细胞的电兴奋性。两种药物对豚鼠细胞均产生剂量依赖性负性肌力反应，但对大鼠细胞，低浓度（<10μM）时首先出现剂量依赖性正性肌力作用，高浓度（>10μM）时则出现负性肌力作用。使用传统电生理技术研究了这些药物影响收缩的可能机制。多不饱和脂肪酸以简单的剂量依赖方式缩短了豚鼠细胞的动作电位时程和平台电位。相反，对大鼠动作电位的影响与肌力作用相似。低浓度（<10μM）时动作电位时程呈浓度依赖性增加，高浓度（>10μM）时则呈浓度依赖性缩短。两种多不饱和脂肪酸均以浓度依赖而非使用依赖的方式降低了两种动物细胞的快钠电流和L型钙电流。在大鼠细胞中，这些药物抑制瞬时外向电流，导致大鼠动作电位时程延长。多不饱和脂肪酸对钙、钠和钾电流的影响是豚鼠和大鼠心脏细胞动作电位这些变化的基础。对L型钙电流和动作电位时程的影响也可以解释这些药物对豚鼠细胞简单的负性肌力作用以及对大鼠细胞更复杂的作用。多不饱和脂肪酸对膜电流的这些影响可能解释了它们的抗心律失常特性。
