Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression
Transient Receptor Potential Canonical Channels Regulate the Induction of Cerebellar Long-Term Depression
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DOI：
10.1523/jneurosci.0073-12.2012
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发表时间：
2012-09-12
影响因子：
5.3
通讯作者：
Kim, Sang Jeong
中科院分区：
文献类型：
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作者：
Chae, Hong Goo;Ahn, Sung Ji;Kim, Sang Jeong
在小脑中，平行纤维和浦肯野细胞之间的突触强度是通过代谢性谷氨酸受体1 （mGluR1）依赖性小脑长期抑制（LTD）来调节的。细胞内钙水平的升高在诱导mglur1依赖性小脑LTD中起重要作用。mGluR1的下游有两个主要的钙来源：瞬时受体电位规范（TRPC）通道和肌醇三磷酸受体（IP3R）。IP3R触发细胞内钙储存的钙释放。在这里，我们发现TRPC通道介导mglur1诱发的慢电流来调节Sprague Dawley大鼠的小脑LTD。我们发现TRPC通道的抑制阻断了小脑LTD的诱导。此外，我们发现，已知的小脑LTD诱导过程，如细胞内钙浓度的增加、蛋白激酶C的激活和GluR2的内化，也会被阻断TRPC所阻碍。这些结果表明mglur1诱发的TRPC通道激活是诱导小脑LTD的必要条件。
In the cerebellum, synaptic strength at the synapses between parallel fibers and Purkinje cells is best known to be modulated via metabotropic glutamate receptor 1 (mGluR1)-dependent cerebellar long-term depression (LTD). An increase in intracellular calcium levels plays an important role in inducing mGluR1-dependent cerebellar LTD. Downstream of mGluR1, there are two major sources of calcium: transient receptor potential canonical (TRPC) channels and inositol trisphosphate receptors (IP3R). IP3R triggers a calcium release from the intracellular calcium store. Here, we show that TRPC channels mediate mGluR1-evoked slow currents to regulate cerebellar LTD in Sprague Dawley rats. We found that the inhibition of TRPC channels blocks the induction of cerebellar LTD. Moreover, we show that processes known to underlie cerebellar LTD induction, such as increases in intracellular calcium concentration, the activation of protein kinase C, and the internalization of GluR2, are also hindered by blocking TRPC. These results suggest that the mGluR1-evoked activation of TRPC channels is required for the induction of cerebellar LTD.