Modulation of Ca2+ cycling in cardiac myocytes by arachidonic acid.
Modulation of Ca2+ cycling in cardiac myocytes by arachidonic acid.
复制标题
花生四烯酸对心肌细胞 Ca2 循环的调节。
DOI：
10.1161/01.res.72.2.376
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发表时间：
1993
影响因子：
20.1
通讯作者：
Bond,M
中科院分区：
文献类型：
--
作者：
Damron,DS;Bond,M
据信，正性肌力药物通过调节 Ca2+ 循环在心肌中发挥作用。然而，磷脂酶激活的参与以及参与正性肌力反应的生化途径仍不清楚。本研究的目的是确定花生四烯酸和/或类二十烷酸是否通过调节心肌细胞中的 Ca2+ 循环来参与正性肌力反应。实验使用新鲜分离的负载 fura-2 的成年大鼠心室肌细胞群进行。花生四烯酸刺激胞质游离 Ca2+ 短暂增加，在添加 EGTA 后仍然存在，但通过咖啡因预处理后显着减少。向电刺激或静止的肌细胞中添加花生四烯酸可增强 ATP 诱导的 Ca2+ 瞬变的幅度。在环加氧酶、脂氧合酶和环氧化酶途径抑制剂存在的情况下，仍然可以观察到这种效应，但在用蛋白激酶 C 抑制剂预处理后，这种效应显着减弱。相反，花生四烯酸减弱了电诱导的 Ca2+ 瞬变的幅度。二十碳四烯酸和 K+ 通道激动剂吡那地尔可模拟这种效应。添加不含脂肪酸的牛血清白蛋白可逆转二十碳四烯酸和花生四烯酸的抑制作用。总之，这些结果表明花生四烯酸可能在心肌兴奋-收缩耦合中发挥生理作用，作为肌膜离子通道和/或肌浆网 Ca2+ 释放的调节剂。
It is believed that inotropic agents exert their effects in cardiac muscle via a modulation of Ca2+ cycling; however, the involvement of phospholipase activation and the biochemical pathways participating in inotropic responsiveness remain unclear. The aim of the current study was to determine whether arachidonic acid and/or eicosanoids participate in inotropic responses by modulating Ca2+ cycling in cardiac myocytes. Experiments were performed with populations of freshly isolated, fura-2-loaded adult rat ventricular myocytes. Arachidonic acid stimulated a transient increase in cytosolic free Ca2+, which was still present after addition of EGTA but was significantly reduced by pretreatment with caffeine. Addition of arachidonic acid to either electrically stimulated or quiescent myocytes enhanced the amplitude of the ATP-induced Ca2+ transient. This effect was still observed in the presence of inhibitors of cyclooxygenase, lipoxygenase, and epoxygenase pathways but was significantly diminished after pretreatment with inhibitors of protein kinase C. In contrast, arachidonic acid attenuated the amplitude of electrically induced Ca2+ transients. This effect was mimicked by eicosatetraynoic acid and by the K+ channel agonist pinacidil. The inhibitory effect of eicosatetraynoic acid and arachidonic acid was reversed by addition of fatty acid-free bovine serum albumin. Together, these results suggest that arachidonic acid may play a physiological role in cardiac muscle excitation-contraction coupling as a modulator of sarcolemmal ion channels and/or Ca2+ release from the sarcoplasmic reticulum.