Protein kinase activator 1-oleoyl-2-acetyl-sn-glycerol inhibits two types of calcium currents in GH3 cells.
Protein kinase activator 1-oleoyl-2-acetyl-sn-glycerol inhibits two types of calcium currents in GH3 cells.
复制标题
蛋白激酶激活剂 1-油酰-2-乙酰基-sn-甘油抑制 GH3 细胞中两种类型的钙电流。
DOI：
10.1152/ajpcell.1988.254.1.c206
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Brown,AM
中科院分区：
文献类型：
--
作者：
Marchetti,C;Brown,AM
许多可兴奋细胞中存在两种类型的 Ca2+ 电流：高阈值、持久或 L 电流和低阈值、瞬时或 T 电流。 L 型 Ca2+ 电流受 β- 和 α- 肾上腺素受体以及细胞内 Ca2+ 等调节，但 T 型 Ca2+ 电流的调节尚不明确。 1-Oleoyl-2-乙酰基-sn-甘油 (OAG) 是一种合成的蛋白激酶 C (PKC) 激活剂，可调节多种可兴奋细胞中的全细胞 Ca2+ 电流。 PKC 激活剂是否优先影响 L 型和 T 型 Ca2+ 电流尚不清楚。我们测试了 OAG 对垂体前叶细胞克隆 GH3 系全细胞 Ca2+ 电流的影响。使用全细胞膜片钳方法测量电流。 4 至 60 microM OAG 可逆地将测试电位产生的 Ca2+ 电流降低至 10 mV，并且在大约 25 microM 时抑制作用达到最大一半。这样的浓度会抑制鸡胚背根神经节 (DRG) 细胞和克隆 AtT-20 垂体细胞中的 Ca2+ 电流。为了测试 OAG 是否优先作用于 L 电流或 T 电流，我们使用去极化预脉冲来使 T 电流失活来将两者分开。 OAG (40 microM) 使 T 电流减弱 60%，使 L 电流减弱 50%。电流波形没有改变，只是简单地缩放，并且对两者的影响发生在应用 OAG 后大约 15 秒。在鸡胚中，DRGs OAG 抑制 T 电流 30%，L 电流抑制 50%。我们得出结论，PKC 通过作用于 L 和 T Ca2+ 通道来调节 Ca2+ 电流。
Two types of Ca2+ currents, high-threshold, long-lasting, or L currents and low-threshold, transient, or T currents, are present in many excitable cells. L-type Ca2+ current is modulated by, among others, beta- and alpha-adrenoreceptors and intracellular Ca2+, but modulation of T-type Ca2+ current is less well established. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), a synthetic activator of protein kinase C (PKC), modulates whole cell Ca2+ currents in a variety of excitable cells. Whether activators of PKC affect preferentially L and T types of Ca2+ currents is unknown. We tested OAGs effects on whole cell Ca2+ currents in the clonal GH3 line of anterior pituitary cells. The currents were measured using the whole cell patch-clamp method. Four to 60 microM OAG reversibly reduced Ca2+ currents produced by test potentials to 10 mV, and the inhibition was half maximal at approximately 25 microM. Such concentrations depress Ca2+ currents in chick embryo dorsal root ganglion (DRG) cells and clonal AtT-20 pituitary cells. To test whether OAG acted preferentially on L or T current, we separated the two using depolarizing prepulses to inactivate T current. OAG (40 microM) attenuated T currents by 60% and L currents by 50%. The current waveforms were not changed and were simply scaled, and the effects on both occurred approximately 15 s after OAG was applied. In chick embryo DRGs OAG inhibited the T current by 30% and the L current by 50%. We conclude that PKC modulates Ca2+ currents by acting on both L and T Ca2+ channels.