Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.
Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.
复制标题
Omega 3 多不饱和脂肪酸调节二氢吡啶对 L 型 Ca2 通道、胞质 Ca2 和成年大鼠心肌细胞收缩的影响。
DOI：
10.1073/pnas.91.19.8832
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发表时间：
1994
影响因子：
11.1
通讯作者：
Lakatta,E
中科院分区：
文献类型：
--
作者：
Pepe,S;Bogdanov,K;Hallaq,H;Spurgeon,H;Leaf,A;Lakatta,E
研究了二十二碳六烯酸（DHA; C22：6）对二氢吡啶（DHP）与离体成年大鼠心肌细胞L型钙通道电流（伊卡）、胞浆钙（Cai）及细胞收缩的相互作用。DHP L型Ca（2+）通道阻断剂尼群地平（10 nM）降低了峰值伊卡（通过全细胞电压钳从-45 mV测量到0 mV），并降低了稳态电刺激（0.5 Hz）期间Ca 2+瞬变的幅度（以indo-1荧光中的瞬变测量，410/490 nm）和抽搐幅度（通过光电二极管阵列测量）。DHP L型Ca 2+通道激动剂BAY K 8644（10 nM）显著增加伊卡，Cai瞬变的幅度和收缩。当细胞同时暴露于DHA（5 μ M）与BAY K 8644或尼群地平时，药物作用被消除。5 μ M的花生四烯酸（C20：4）既不能阻断尼群地平的抑制作用，也不能阻止BAY K 8644的增强作用。DHA对DHP作用的调节可以通过用1 mg/ml的无脂肪酸牛血清白蛋白进行细胞灌注来逆转。无论是DHA还是花生四烯酸单独（5 μ M）对测量的参数都没有任何明显的影响。DHA（5 μ M）对β-肾上腺素能受体刺激（异丙肾上腺素，0.01-1 μ M）诱导的伊卡、Cai或收缩增加没有影响。DHA抑制DHP激动剂和拮抗剂对Ca（2+）通道电流的作用，但单独或对β-肾上腺素能诱导的伊卡增加无作用，这一发现表明DHA在DHP结合位点或附近特异性结合Ca 2+通道，并干扰伊卡调节。
The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (ICa), cytosolic Ca2+ (Cai), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca(2+)-channel blocker nitrendipine (10 nM) reduced peak ICa (measured by whole-cell voltage clamp from -45 to 0 mV) and reduced the amplitude of the Ca2+ transient (measured as the transient in indo-1 fluorescence, 410/490 nm) and the twitch amplitude (measured via photodiode array) during steady-state electrical stimulation (0.5 Hz). The DHP L-type Ca2+ channel agonist BAY K 8644 (10 nM) significantly increased ICa, the amplitude of the Cai transient, and contraction. When cells were exposed to DHA (5 microM) simultaneously with either BAY K 8644 or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5 microM did not block the inhibitory effects of nitrendipine nor did it prevent the potentiating effects of BAY K 8644. DHA modulation of DHP action could be reversed by cell perfusion with fatty acid-free bovine serum albumin at 1 mg/ml. Neither DHA nor arachidonic acid alone (5 microM) had any apparent effect on the parameters measured. DHA (5 microM) had no influence over beta-adrenergic receptor stimulation (isoproterenol, 0.01-1 microM)-induced increases in ICa, Cai, or contraction. The findings that DHA inhibits the effect of DHP agonists and antagonists on Ca(2+)-channel current but has no effect alone or on beta-adrenergic-induced increases in ICa suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with ICa modulation.