Effects of fatty acids on BK channels in GH3 cells
Effects of fatty acids on BK channels in GH3 cells
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DOI：
10.1152/ajpcell.2000.279.4.c1211
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发表时间：
2000-10-01
影响因子：
5.5
通讯作者：
Eaton, DC
中科院分区：
文献类型：
--
作者：
Denson, DD;Wang, XP;Eaton, DC
GH(3) 细胞中 Ca2+ 激活的 K+ (BK) 通道由花生四烯酸 (AA) 激活。由于胞质磷脂酶 A(2) 可以产生其他不饱和游离脂肪酸 (FFA)，因此我们检查了 FFA 对切除斑块中 BK 通道的影响。控制记录是在几个保持电位下进行的。将所需的 FFA 添加到浴溶液中，并重复电压范例。 AA 使 BK 通道的活性增加 3.6 +/- 1.6 倍。顺式 FFA、棕榈油酸、油酸、亚油酸、亚麻酸、二十碳五烯酸和 AA 的三键类似物二十碳四烯酸均会增加 BK 通道活性，而硬脂酸（饱和）或反式异构体反油酸、亚油酸和亚麻油酸则没有效果。顺式不饱和 FFA 将开路概率与电压关系向左移动，斜率没有变化，表明电压传感器的灵敏度没有变化。膜流动性的测量显示膜流动性的变化与 BK 通道激活的变化之间没有相关性。此外，在 N-乙酰半胱氨酸存在的情况下，AA 对 BK 通道的影响不受影响。花生四烯酰辅酶 A 是 AA 的一种膜不可渗透类似物，当应用于切除斑块的胞质表面时，会激活通道，这表明来自 BK 通道胞质表面的 FFA 的作用。我们的数据表明顺式 FFA 和 BK 通道蛋白之间存在直接相互作用。
Ca2+-activated K+ (BK) channels in GH(3) cells are activated by arachidonic acid (AA). Because cytosolic phospholipase A(2) can produce other unsaturated free fatty acids (FFA), we examined the effects of FFA on BK channels in excised patches. Control recordings were made at several holding potentials. The desired FFA was added to the bath solution, and the voltage paradigm was repeated. AA increased the activity of BK channels by 3.6 +/- 1.6-fold. The cis FFA, palmitoleic, oleic, linoleic, linolenic, eicosapentaenoic, and the triple bond analog of AA, eicosatetraynoic acid, all increased BK channel activity, whereas stearic (saturated) or the trans isomers elaidic, linolelaidic, and linolenelaidic had no effect. The cis unsaturated FFA shifted the open probability vs. voltage relationships to the left without a change in slope, suggesting no change in the sensitivity of the voltage sensor. Measurements of membrane fluidity showed no correlation between the change of membrane fluidity and the change in BK channel activation. In addition, AA effects on BK channels were unaffected in the presence of N-acetyl-cysteine. Arachidonyl-CoA, a membrane impermeable analog of AA, activates channels when applied to the cytosolic surface of excised patches, suggesting an effect of FFAs from the cytosolic surface of BK channels. Our data imply a direct interaction between cis FFA and the BK channel protein.