Glucocorticoids prolong Ca2+ transients in hippocampal-derived H19-7 neurons by repressing the plasma membrane Ca2+-ATPase-1
Glucocorticoids prolong Ca2+ transients in hippocampal-derived H19-7 neurons by repressing the plasma membrane Ca2+-ATPase-1
复制标题
DOI：
10.1210/me.16.7.1629
复制
发表时间：
2002-07-01
影响因子：
--
通讯作者：
Pearce, D
中科院分区：
文献类型：
--
作者：
Bhargava, A;Mathias, RS;Pearce, D
钙离子（Ca 2+）在介导细胞一系列结构和功能反应方面发挥着重要作用。在海马神经元中，糖皮质激素（GC）水平升高，如在应激期间所见，扰乱钙稳态并导致神经元兴奋性和活力改变。配体门控和电压门控钙通道一直是激素调节的假定目标;然而，间接证据表明钙挤出可能是GC调节的重要目标。在此，我们证明了GC诱导的质膜Ca ~（2+）-ATP酶-1（PMCA 1）的抑制是培养的海马H19-7细胞内Ca ~（2+）水平（[Ca ~（2+）除以]（i））的一个重要决定因素。特别地，GC处理引起激动剂诱发的[Ca ~（2+）]（i）升高的延长，而外源性PMCA 1的表达阻止了这种升高。此外，使用RNA干扰技术选择性抑制PMCA 1导致在不存在GC处理的情况下延长Ca 2+瞬变。综上所述，这些观察结果表明，GC介导的PMCA 1的抑制是必要的和足够的，以增加激动剂诱发的Ca 2+瞬变通过下调Ca 2+挤出机制的情况下，对钙通道的影响。长期暴露于GC，导致[Ca 2 +]（i）的伴随蓄积，可能会损害神经元功能和活力。
Calcium ions (Ca2+) play an important role in mediating an array of structural and functional responses in cells. In hippocampal neurons, elevated glucocorticoid (GC) levels, as seen during stress, perturb calcium homeostasis and result in altered neuronal excitability and viability. Ligand- and voltage-gated calcium channels have been the presumed targets of hormonal regulation; however, circumstantial evidence has suggested the possibility that calcium extrusion might be an important target of GC regulation. Here we demonstrate that GC-induced repression of the plasma membrane Ca2+-ATPase-1 (PMCA1) is an essential determinant of intracellular Cal(2+) levels ([Ca-2divided by](i)) in cultured hippocampal H19-7 cells, In particular, GC treatment caused a prolongation of agonist-evoked elevation of [Ca2+](i) that was prevented by the expression of exogenous PMCA1. Furthermore, selective inhibition of PMCA1 using the RNA interference technique caused prolongation of Ca2+ transients in the absence of GC treatment. Taken together, these observations suggest that GC-mediated repression of PMCA1 is both necessary and sufficient to increase agonist-evoked Ca2+ transients by down-regulating Ca2+ extrusion mechanisms in the absence of effects on calcium channels. Prolonged exposure to GCs, resulting in concomitant accumulation of [Ca2+](i), is likely to compromise neuronal function and viability.