Calcium transport mechanisms of PC12 cells.
Calcium transport mechanisms of PC12 cells.
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DOI：
10.1085/jgp.200709915
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发表时间：
2008-04
期刊：
影响因子：
--
通讯作者：
Hille B
中科院分区：
文献类型：
--
作者：
Duman JG;Chen L;Hille B
许多Ca2+信号传导的研究使用PC12细胞，但这些细胞中Ca2+清除机制的平衡是未知的。我们使用Ca2+转运体的药理抑制来表征未分化和神经生长因子分化的PC12细胞去极化后的Ca2+清除。在两种细胞状态下，肌内质网Ca2+ atp酶（SERCA）、质膜Ca2+ atp酶（PMCA）和Na+/Ca2+交换器（NCX）几乎占据了所有Ca2+清除的位置，其中NCX和PMCA的贡献最大。线粒体单转运蛋白的贡献很小。在分散线粒体质子梯度的物质存在下，分化细胞的ATP池比未分化细胞的ATP池更不稳定。分化的PC12细胞有少量的Ca2+清除成分，具有与分泌途径Ca2+ atp酶（SPCA）一致的药理学特征，可能存在于高尔基体和/或分泌颗粒上。未分化细胞和分化细胞在整体Ca2+运输和SERCA引起的小运输方面相似，但它们在PMCA和NCX运输的比例上有所不同。分化后的PC12细胞的神经突运输与躯体运输在性质上相似，不同之处在于神经突中储存的ER有时会释放Ca2+，而不是在去极化后将其清除。我们制定了一个数学模型来模拟观察到的Ca2+清除，并定量描述这些未分化和ngf分化状态之间的差异。该模型需要一个PC12细胞质内源性Ca2+结合比的值，我们测量的值为268±85。我们的研究结果表明，Ca2+在未分化的PC12细胞中的转运与肾上腺染色质细胞中的转运非常不同，它们通常被认为是模型。这两种细胞状态的转运更接近交感神经元的转运，因此分化的PC12细胞通常被认为是交感神经元的模型。与其他细胞类型的比较表明，不同的细胞强调不同的Ca2+转运机制。
Many studies of Ca2+ signaling use PC12 cells, yet the balance of Ca2+ clearance mechanisms in these cells is unknown. We used pharmacological inhibition of Ca2+ transporters to characterize Ca2+ clearance after depolarizations in both undifferentiated and nerve growth factor-differentiated PC12 cells. Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA), plasma membrane Ca2+ ATPase (PMCA), and Na+/Ca2+ exchanger (NCX) account for almost all Ca2+ clearance in both cell states, with NCX and PMCA making the greatest contributions. Any contribution of mitochondrial uniporters is small. The ATP pool in differentiated cells was much more labile than that of undifferentiated cells in the presence of agents that dissipated mitochondrial proton gradients. Differentiated PC12 cells have a small component of Ca2+ clearance possessing pharmacological characteristics consistent with secretory pathway Ca2+ ATPase (SPCA), potentially residing on Golgi and/or secretory granules. Undifferentiated and differentiated cells are similar in overall Ca2+ transport and in the small transport due to SERCA, but they differ in the fraction of transport by PMCA and NCX. Transport in neurites of differentiated PC12 cells was qualitatively similar to that in the somata, except that the ER stores in neurites sometimes released Ca2+ instead of clearing it after depolarization. We formulated a mathematical model to simulate the observed Ca2+ clearance and to describe the differences between these undifferentiated and NGF-differentiated states quantitatively. The model required a value for the endogenous Ca2+ binding ratio of PC12 cell cytoplasm, which we measured to be 268 ± 85. Our results indicate that Ca2+ transport in undifferentiated PC12 cells is quite unlike transport in adrenal chromaffin cells, for which they often are considered models. Transport in both cell states more closely resembles that of sympathetic neurons, for which differentiated PC12 cells often are considered models. Comparison with other cell types shows that different cells emphasize different Ca2+ transport mechanisms.
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影响因子：
7.7
作者：
Chen, LY;Koh, DS;Hille, B
通讯作者：
Hille, B
DOI：
10.1016/j.bbamcr.2004.10.013
发表时间：
2005-05-15
影响因子：
5.1
作者：
Kubota, T;Shindo, Y;Oka, K
通讯作者：
Oka, K
影响因子：
10.4
作者：
Bozulic, L. D.;Malik, M. T.;Dean, W. L.
通讯作者：
Dean, W. L.
影响因子：
16.2
作者：
Herrington, J;Park, YB;Hille, B
通讯作者：
Hille, B
影响因子：
4.4
作者：
DAVIS, LH;KAUFFMAN, FC
通讯作者：
KAUFFMAN, FC