CaV2 channel subtype expression in rat sympathetic neurons is selectively regulated by α2δ subunits.
CaV2 channel subtype expression in rat sympathetic neurons is selectively regulated by α2δ subunits.
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CaV2 通道亚型表达在大鼠交感神经元中选择性地受α2β 亚基调节。
DOI：
10.1080/19336950.2017.1356954
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Kammermeier,PaulJ
中科院分区：
文献类型：
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作者：
Scott,MalloryB;Kammermeier,PaulJ
2型电压门控钙离子通道是神经元突触前神经传递的主要介质，但其在神经索马体的功能在调节兴奋性方面也很重要。CaV 2通道在突触中表达的调节机制已被广泛研究，这促使我们在索马中进行类似的研究。来自上级颈神经节（SCG）的大鼠交感神经元天然表达CaV 2.2和CaV 2.3。我们以前注意到，CaV2.1而不是CaV2.2的异源表达导致SCG神经元中钙电流增加。在本研究中，我们扩展了这些观察结果，表明CaV2.1和CaV2.3的表达导致钙电流增加，而CaV2.2的表达没有。此外，CaV2.1可以取代天然CaV2.2通道，但CaV2.3表达不能。单独的辅助亚基α2δ-1、α2δ-2、α2δ-3或β4的异源表达不能增加电流密度，表明CaV2.2过表达时的钙电流上限不是由于缺乏这些亚基。有趣的是，重组α2δ亚基的引入对重组通道置换天然CaV2.2产生了令人惊讶的效果。α2δ-1和α2δ-2似乎都通过重组通道表达促进CaV2.2置换，而α2δ-3似乎保护CaV2.2免于置换。因此，我们观察到特异性α2δ亚基对神经元中CaV通道功能表达的选择性优先化。这些数据突出了α2δ亚型的新功能，可以阐明CaV 2膜表达的亚型选择性。
Type two voltage gated calcium (CaV2) channels are the primary mediators of neurotransmission at neuronal presynapses, but their function at neural soma is also important in regulating excitability. Mechanisms that regulate CaV2 channel expression at synapses have been studied extensively, which motivated us to perform similar studies in the soma. Rat sympathetic neurons from the superior cervical ganglion (SCG) natively express CaV2.2 and CaV2.3. We noted previously that heterologous expression of CaV2.1 but not CaV2.2 results in increased calcium current in SCG neurons. In the present study, we extended these observations to show that both CaV2.1 and CaV2.3 expression resulted in increased calcium currents while CaV2.2 expression did not. Further, CaV2.1 could displace native CaV2.2 channels, but CaV2.3 expression could not. Heterologous expression of the individual accessory subunits α2δ-1, α2δ-2, α2δ-3, or β4 alone failed to increase current density, suggesting that the calcium current ceiling when CaV2.2 was over-expressed was not due to lack of these subunits. Interestingly, introduction of recombinant α2δ subunits produced surprising effects on displacement of native CaV2.2 by recombinant channels. Both α2δ-1 and α2δ-2 seemed to promote CaV2.2 displacement by recombinant channel expression, while α2δ-3 appeared to protect CaV2.2 from displacement. Thus, we observe a selective prioritization of CaVchannel functional expression in neurons by specific α2δ subunits. These data highlight a new function for α2δ subtypes that could shed light on subtype selectivity of CaV2 membrane expression.