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

膳食中多不饱和脂肪酸的抗肿瘤作用 近年来已经观察到掺入心脏细胞膜 年作用机制尚待确定。本工程 无膜多不饱和脂肪酸递送到离体 研究了成年大鼠心肌细胞（在体内，这些细胞可以被释放 来自磷脂酶作用后的心脏细胞膜）。本 一项研究调查了DHA和花生四烯酸（AA; C20：4，n-6）对 全细胞电压钳中L型钙和K+通道电导的研究 实验和细胞内游离钙荧光和收缩 成年大鼠indo-1负载的心肌细胞。 尼群地平（10 nM）减少豌豆 ICa，通过全细胞钳测量，从-40 mV至-5 mV，颤搐收缩 振幅和相关的胞质indo-1 Ca2+荧光测量期间 电刺激（0.5Hz）。DHA（5fM）可消除这些效应，但AA（5fM）可消除这些效应。 不阻断尼群地平的作用。用10 nM BAYK8644进行的实验导致 在增加抽搐收缩和相关的细胞溶质钙，这可能是B DHA而不是AA（图2）。单独使用DHA或AA没有效果。既不 DHA和AA均不改变异丙肾上腺素（1，0.5，0.1fM）诱导的ICa增加， 抽搐幅度DHA消除尼群地平或BAYK 8644的作用， 没有单独的影响，表明它结合附近的Ca2+通道 二氢吡啶结合位点，并通过 二氢吡啶。 而DHA对内向整流电流（Ik1）无影响 和延迟整流电流（Ik），它加速了失活 瞬时外向K+电流（Ito），并降低其幅度。 这些 结果表明，选择性阻断Ito和与 omega-3 PUFA对心肌细胞二氢吡啶受体的保护作用 Ca~（2+）超载和缺血诱发心律失常。 该动作可以 参与鱼油饮食在体内的抗肿瘤作用， 动物模型和患有冠状动脉疾病的人。

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 project 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) o L-type calcium and K+ channel conductance in whole cell voltage-clamp experiments and on cytosolic free calcium fluorescence and contraction in adult rat indo-1 loaded cardiac myocytes. Nitrendipine (10 nM) reduced pea 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 (5fM) abolished these effects but AA di not block the nitrendipine effects. Experiments with 10nM BAYK8644 resulted in increased twitch contraction and related cytosolic calcium which could b prevented by DHA but not AA (Fig2). DHA or AA alone had no effect. Neither DHA nor AA altered isoproterenol (1, 0.5, 0.1fM) induced increases in ICa o 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. While DHA has no effect on inward rectifier current (Ik1 and delayed rectifier current (Ik) it accelerates the inactivation of transient outward K+ current (Ito) and decreases its magnitude. These results suggest that selective blockade of Ito and also binding to the dihydropyridine receptor in heart cells by omega-3 PUFA may protect agonist Ca2+ overload and ischemia induced arrhythmias. 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.