Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts.
Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts.
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DOI：
10.1152/ajpcell.1993.265.5.c1239
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发表时间：
1993-11
期刊：
影响因子：
--
通讯作者：
Z. Wang;M. Estacion;L. Mordan
中科院分区：
文献类型：
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作者：
Z. Wang;M. Estacion;L. Mordan
研究低阈值电压门控钙通道(VGCC)在血小板衍生生长因子(PDGF)刺激的C3H/10T1/2小鼠成纤维细胞中对细胞外钙内流和细胞增殖的调节作用。以往的研究表明，PDGF刺激后的细胞周期进程依赖于细胞外钙内流，导致细胞内钙离子浓度持续增加。去甲二氢愈创木酸是血管内皮细胞钙内流的阻断剂，可抑制血小板衍生生长因子诱导的细胞内钙内流、细胞内持续钙升高以及向S时相的转化。使用全细胞膜片钳技术测量钙电流，NDGA抑制低阈值VGCC的内向钙电流，VGCC是唯一在C3H/10T1/2成纤维细胞中表达的VGCC。NDGA对钙内流和细胞增殖的抑制作用平均剂量为2-3微米。虽然NDGA也能有效地抑制环氧合酶和脂氧合酶，但前列腺素或白三烯的加入不能逆转这种抑制作用，也不能被其他抗氧化剂复制。这些数据支持低阈值VGCC在PDGF刺激细胞增殖的过程中介导细胞外钙内流的假说。
The role of low-threshold voltage-gated calcium channels (VGCC) in modulating extracellular calcium influx and proliferation was investigated in platelet-derived growth factor (PDGF)-stimulated C3H/10T1/2 mouse fibroblasts. Previous studies demonstrated that cell cycle progression after PDGF stimulation was dependent on extracellular calcium influx producing a sustained increase in the intracellular calcium concentration. In this study, PDGF-induced calcium influx, the sustained intracellular calcium increase, and progression to S phase were inhibited by nordihydroguariaretic acid (NDGA), an inhibitor of calcium influx through VGCC. With the use of the whole cell patch-clamp technique to measure calcium currents, NDGA inhibited inward calcium current through low-threshold VGCC, the only VGCC expressed in C3H/10T1/2 fibroblasts. The inhibitory effects of NDGA on calcium influx and cell proliferation each had a mean inhibitory dose of 2-3 microM. Although NDGA also effectively inhibits cyclooxygenase and lipoxygenase, the addition of prostaglandins or leukotrienes could not reverse this inhibition nor could it be replicated by other antioxidants. These data support the hypothesis that low-threshold VGCC can mediate extracellular calcium influx on the stimulation of cell proliferation by PDGF.