Methamphetamine acutely inhibits voltage-gated calcium channels but chronically up-regulates L-type channels.
Methamphetamine acutely inhibits voltage-gated calcium channels but chronically up-regulates L-type channels.
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DOI：
10.1111/jnc.13104
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发表时间：
2015-07
影响因子：
4.7
通讯作者：
Chang L
中科院分区：
文献类型：
--
作者：
Andres MA;Cooke IM;Bellinger FP;Berry MJ;Zaporteza MM;Rueli RH;Barayuga SM;Chang L
在神经元中，钙（Ca 2+）通道调节从突触传递到基因表达的各种功能。它们还诱导神经可塑性变化，改变精神兴奋剂给药后的基因表达。钙离子通道阻滞剂因其能够减少甲基苯丙胺（METH）使用者的药物渴求而被认为是治疗METH依赖的潜在治疗药物。在这里，我们研究了METH暴露对电压门控性钙通道的影响，使用SH-SY 5 Y细胞作为多巴胺能神经元的模型。我们发现METH具有不同的短期和长期影响。短期效应包括立即（<5分钟）直接抑制Ca 2+离子通过Ca 2+通道的运动。长时间暴露于METH（20分钟或48小时）选择性上调仅CACNA 1C基因的表达，从而增加L-型Ca 2+通道的数量。CACNA 1C的这种上调与CREB（cAMP反应元件结合蛋白）（CACNA 1C基因表达的已知调节剂）和MYC基因的表达相关，MYC基因编码一种转录因子，该转录因子与CACNA 1C基因转录起始位点的近端结合。Ca 2+离子运动的短期抑制和随后的Ca 2+通道基因表达的上调共同表明CREB和C-MYC介导的机制的操作，以补偿METH对Ca 2+通道的抑制。Ca 2+电流密度增加和随后的细胞内Ca 2+增加可能有助于伴随慢性METH滥用的神经变性。
In neurons, calcium (Ca2+) channels regulate a wide variety of functions ranging from synaptic transmission to gene expression. They also induce neuroplastic changes that alter gene expression following psychostimulant administration. Ca2+ channel blockers have been considered as potential therapeutic agents for the treatment of methamphetamine (METH) dependence because of their ability to reduce drug craving among METH users. Here, we studied the effects of METH exposure on voltage-gated Ca2+ channels using SH-SY5Y cells as a model of dopaminergic neurons. We found that METH has different short- and long-term effects. A short-term effect involves immediate (<5 min) direct inhibition of Ca2+ ion movements through Ca2+ channels. Longer exposure to METH (20 min or 48 hr) selectively upregulates the expression of only the CACNA1C gene, thus increasing the number of L-type Ca2+ channels. This upregulation of CACNA1C is associated with the expression of the CREB (cAMP responsive element binding protein), a known regulator of CACNA1C gene expression, and the MYC gene, which encodes a transcription factor that putatively binds to a site proximal to the CACNA1C gene transcription initiation site. The short-term inhibition of Ca2+ ion movement and later, the upregulation of Ca2+ channel gene expression together suggest the operation of CREB- and C-MYC-mediated mechanisms to compensate for Ca2+ channel inhibition by METH. Increased Ca2+ current density and subsequent increased intracellular Ca2+ may contribute to the neurodegeneration accompanying chronic METH abuse.
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DOI：
10.1016/j.bbrc.2009.04.150
发表时间：
2009-07-10
影响因子：
3.1
作者：
Karnabi, Eddy;Qu, Yongxia;Mancarella, Salvatore;Yue, Yuankun;Wadgaonkar, Raj;Boutjdir, Mohamed
通讯作者：
Boutjdir, Mohamed
影响因子：
3.7
作者：
Han W;Takamatsu Y;Yamamoto H;Kasai S;Endo S;Shirao T;Kojima N;Ikeda K
通讯作者：
Ikeda K
影响因子：
5.3
作者：
Rajadhyaksha, A;Husson, I;Kosofsky, BE
通讯作者：
Kosofsky, BE
影响因子：
4.8
作者：
Goodwin, J. Shawn;Larson, Gaynor A.;Khoshbouei, Habibeh
通讯作者：
Khoshbouei, Habibeh
影响因子：
64.5
作者：
Gomez-Ospina, Natalia;Tsuruta, Fuminori;Dolmetsch, Ricardo
通讯作者：
Dolmetsch, Ricardo