FATTY ACID MODULATION OF L-TYPE CALCIUM CHANNEL FUNCTION IN CARDIAC MYOCYTES

饮食后多不饱和脂肪酸的抗心律失常作用 最近观察到心肌细胞膜的掺入 好几年了。其作用机制尚待确定。在这项研究中 无膜多不饱和脂肪酸传递给人的影响 对分离的成年大鼠心肌细胞进行了研究(这些细胞可以在体内 磷脂酶后从心肌细胞膜上释放 行动)。本研究调查了DHA和DHA的作用。 花生四烯酸对L型钙通道电导的影响 全细胞电压钳实验及细胞内游离钙的变化 成年大鼠INDO-1负荷心脏的荧光和收缩 肌细胞。DHA对二氢吡啶与钙离子相互作用的影响 分离的心肌细胞的通道电流(ICa)和抽动收缩(25 摄氏度)。尼群地平(10 NM)降低ICa峰， 由全细胞钳位测量，从-40 mV到-5 mV，抽搐收缩 测量的幅度和相关的胞浆Indo-1钙离子荧光 在电刺激(0.5赫兹)时。废除DHA(5微摩尔) 但AA不能阻断尼群地平的作用。 用10 nm BAYK8644进行的实验导致了更多的抽动收缩 和相关的胞浆钙，DHA可以预防，但不能 AA(图2)。DHA或AA单独作用不明显。DHA和AA均未改变 异丙肾上腺素(1，0.5，0.1微摩尔)引起的ICa或 抽动幅度。DHA取消尼群地平或BAYK8644的作用 但没有单独作用，表明它与钙离子通道 二氢吡啶结合部位并干扰ICA的调节 二氢吡啶类化合物。这一作用可能与抗心律失常有关。 鱼油饲料对动物体内和人体内的影响 患有冠状动脉疾病。

Antiarrhythmic effects of polyunsaturated fatty acids following dietary incorporation into cardiac cell membranes have been observed in recent years. The mechanisms of action are yet to be defined. In this study the effect of membrane-free polyunsaturated fatty acids delivered to isolated adult rat cardiac myocytes was investigated (in vivo these can be released from cardiac cell membranes following phospholipase action). The present study investigates the effects of DHA and arachidonic acid (AA;C20:4,n-6) on L-type calcium channel conductance in whole cell voltage-clamp experiments and on cytosolic free calcium fluorescence and contraction in adult rat indo-1 loaded cardiac myocytes. The effect of DHA on dihydropyridine interaction with Ca2+ channel current (ICa) and twitch contraction in isolated myocytes (25 degrees C) was measured. Nitrendipine (10 nM) reduced peak ICa, measured by whole cell clamp from -40 to -5 mV, twitch contraction amplitude and associated cytosolic indo-1 Ca2+ fluorescence measured during electrical stimulation (0.5Hz). DHA (5 micromoles) abolished these effects but AA did not block the nitrendipine effects. Experiments with 10nM BAYK8644 resulted in increased twitch contraction and related cytosolic calcium which could be prevented by DHA but not AA (Fig2). DHA or AA alone had no effect. Neither DHA nor AA altered isoproterenol (1, 0.5, 0.1 micromoles) induced increases in ICa or twitch amplitude. That DHA abolishes nitrendipine or BAYK8644 effects but has no effect alone, suggests that it binds to Ca2+ channels near dihydropyridine binding sites and interferes with ICa modulation by dihydropyridines. This action may be involved in the antiarrhythmic effects of fish oil diet in vivo both in animal models and in humans with coronary artery disease.