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首页> 外文期刊>The European Journal of Neuroscience >Ca1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB.
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Ca1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREB.

机译：Ca1.2和CaV1.3神经元L型钙通道：差异靶向和pCREB的信号。

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摘要

Neurons express multiple types of voltage-gated calcium (Ca2+) channels. Two subtypes of neuronal L-type Ca2+ channels are encoded by CaV1.2 and CaV1.3 pore-forming subunits. To compare targeting of CaV1.2 and CaV1.3 L-type Ca2+ channels, we transfected rat hippocampal neuronal cultures with surface-epitope-tagged sHA-CaV1.2 or sHA-CaV1.3a constructs and found that: (i) both sHA-CaV1.2 and sHA-CaV1.3a form clusters on the neuronal plasma membrane surface; (ii) when compared with sHA-CaV1.2 surface clusters, the sHA-CaV1.3a surface clusters were 10% larger and 25% brighter, but 35% less abundant; (iii) 81% of sHA-CaV1.2 surface clusters, but only 48% of sHA-CaV1.3a surface clusters, co-localized with synapsin clusters; (iv) co-expression with GFP-Shank-1B had no significant effect on sHA-CaV1.2 surface clusters, but promoted formation and synaptic localization of sHA-CaV1.3a surface clusters. In experiments with dihydropyridine-resistant CaV1.2 and CaV1.3a mutants we demonstrated that CaV1.3a L-type Ca2+ channels preferentially mediate nuclear pCREB signaling in hippocampal neurons at low, but not at high, levels of stimulation. In experiments with primary neuronal cultures from CaV1.3 knockout mice we discovered that CaV1.3 channels play a more important role in pCREB signaling in striatal medium spiny neurons than in hippocampal neurons. Our results provide novel insights into the function of CaV1.2 and CaV1.3 L-type Ca2+ channels in the brain.
机译：神经元表达多种类型的电压门控钙（Ca2 +）通道。神经元L型Ca2 +通道的两个亚型由CaV1.2和CaV1.3孔形成亚基编码。为了比较针对CaV1.2和CaV1.3 L型Ca2 +通道的靶向性，我们用表面表位标记的sHA-CaV1.2或sHA-CaV1.3a构建体转染了大鼠海马神经元培养物，发现： -CaV1.2和sHA-CaV1.3a在神经元质膜表面形成簇; （ii）与sHA-CaV1.2表面簇相比，sHA-CaV1.3a表面簇大10％，增亮25％，但丰富度降低35％; （iii）与突触素簇共定位的81％sHA-CaV1.2表面簇，但只有48％sHA-CaV1.3a表面簇; （iv）与GFP-Shank-1B的共表达对sHA-CaV1.2表面簇无明显影响，但促进sHA-CaV1.3a表面簇的形成和突触定位。在对二氢吡啶抗性CaV1.2和CaV1.3a突变体进行的实验中，我们证明了CaV1.3a L型Ca2 +通道在低水平（但不是高水平）刺激下优先介导海马神经元中的核pCREB信号传导。在用来自CaV1.3敲除小鼠的原代神经元培养物进行的实验中，我们发现CaV1.3通道在纹状体中棘神经元中的pCREB信号传导中比在海马神经元中发挥更重要的作用。我们的结果提供了对大脑中CaV1.2和CaV1.3 L型Ca2 +通道功能的新颖见解。

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