L-TYPE VOLTAGE-SENSITIVE CALCIUM CHANNELS MEDIATE SYNAPTIC ACTIVATION OF IMMEDIATE EARLY GENES
L-TYPE VOLTAGE-SENSITIVE CALCIUM CHANNELS MEDIATE SYNAPTIC ACTIVATION OF IMMEDIATE EARLY GENES
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DOI：
10.1016/0896-6273(91)90375-a
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发表时间：
1991-10-01
期刊：
影响因子：
16.2
通讯作者：
BARABAN, JM
中科院分区：
文献类型：
--
作者：
MURPHY, TH;WORLEY, PF;BARABAN, JM
尽管L型电压敏感性钙通道（VSCC）的电生理特征已得到很好的表征，但它们在突触生理学中的作用仍不清楚。为了评估它们参与突触调控基因表达，我们研究了选择性VSCC拮抗剂对培养的皮层神经元中几种转录因子基因的基础、突触介导的激活的影响。暴露于L型VSCC拮抗剂可迅速抑制c-fos、jun-B、zif 268和fos-B的基础表达，而VSCC激动剂（-）BayK-8644可增加c-fos、jun-B、zif 268和fos-B的基础表达。尽管VSCC拮抗剂阻断红藻氨酸诱导的细胞内钙和基因表达的升高，但这些药物对这些神经元中自发电活动或突触诱导的钙瞬变几乎没有影响。这些研究结果表明，即使L型VSCC贡献突触钙瞬变的相对较小的组件，他们似乎发挥了关键作用，在耦合突触兴奋激活的转录事件被认为有助于神经元的可塑性。
Although L-type voltage-sensitive calcium channels (VSCCs) have been well characterized electrophysiologically, their role in synaptic physiology has remained unclear. To assess their involvement in synaptic regulation of gene expression, we have examined the effects of selective VSCC antagonists on basal, synaptically mediated activation of several transcription factor genes in cultured cortical neurons. Basal expression of c-fos, jun-B, zif268, and fos-B is rapidly suppressed by exposure to L-type VSCC antagonists and increased by (-)BayK-8644, a VSCC agonist. Although VSCC antagonists block kainate-induced rises in intracellular calcium and gene expression, these agents have little effect on spontaneous electrical activity or synaptically induced calcium transients in these neurons. These findings suggest that even though L-type VSCCs contribute a relatively minor component of synaptic calcium transients, they appear to play a key role in coupling synaptic excitation to activation of transcriptional events thought to contribute to neuronal plasticity.