Department of Physiology, Biomedical Science, College of Medicine, Seoul National University, Chongro-gu, Seoul 110-799, Korea.
J Neurosci. 2012 Sep 12;32(37):12909-14. doi: 10.1523/JNEUROSCI.0073-12.2012.
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 (IP(3)R). IP(3)R 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.
在小脑，平行纤维和浦肯野细胞之间突触的突触强度，通过代谢型谷氨酸受体 1（mGluR1）依赖性小脑长时程抑制（LTD）被认为是最佳调制的。细胞内钙离子水平的增加在诱导 mGluR1 依赖性小脑 LTD 中起着重要作用。mGluR1 的下游有两个主要的钙离子来源：瞬时受体电位经典通道（TRPC）和三磷酸肌醇受体（IP（3）R）。IP（3）R 触发细胞内钙库的钙释放。在这里，我们表明 TRPC 通道介导 mGluR1 诱导的慢电流来调节 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，我们表明，已知的小脑 LTD 诱导过程，如细胞内钙离子浓度的增加、蛋白激酶 C 的激活和 GluR2 的内化，也被阻断 TRPC 所阻碍。这些结果表明，mGluR1 诱导的 TRPC 通道的激活是小脑 LTD 诱导所必需的。
