Local calcium signalling by inositol-1,4, 5-trisphosphate in Purkinje cell dendrites
Local calcium signalling by inositol-1,4, 5-trisphosphate in Purkinje cell dendrites
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DOI：
10.1038/25541
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发表时间：
1998-12-31
期刊：
影响因子：
64.8
通讯作者：
Augustine, GJ
中科院分区：
文献类型：
--
作者：
Finch, EA;Augustine, GJ
第二信使肌醇-1，4，5-三磷酸（InsP（3））通过激活细胞内Ca 2+储存膜上的特异性受体从这些储存中释放Ca 2+（1）。在许多细胞中，InsP（3）是一种全局信号分子，在整个细胞质中释放Ca 2+（1，2）。然而，在神经元中，情况可能不同（3，4），因为突触活动可能在离散位置产生InsP（3）。在这里，我们描述了突触后小脑浦肯野神经元中的InsP（3）信号传导，该神经元具有高水平的InsP（3）受体（5）。我们发现，重复激活平行纤维和浦肯野细胞之间的突触，导致浦肯野细胞中InsP（3）介导的Ca ~（2+）释放。这种Ca 2+释放仅限于单个突触后棘，其中代谢型谷氨酸受体（6，7）和InsP 3受体（5）都位于此处，或者仅限于多个棘和相邻的树突干。浦肯野细胞树突中笼状InsP（3）（参考文献8）的局灶性光解也产生Ca 2+信号，其仅从InsP（3）产生部位传播几微米。非笼状InsP（3）产生一个持久的抑制平行纤维突触传递，仅限于突触的Ca 2+浓度升高。因此，在浦肯野细胞中，InP 3在有限的空间范围内起作用，使其能够调节局部平行纤维突触组的功能。
The second messenger inositol-1,4,5-trisphosphate (InsP(3)) releases Ca2+ from intracellular Ca2+ stores by activating specific receptors on the membranes of these stores(1). In many cells, InsP(3) is a global signalling molecule that liberates Ca2+ throughout the cytoplasm(1,2) . However, in neurons the situation might be different(3,4), because synaptic activity may produce InsP(3) at discrete locations. Here we characterize InsP(3) signalling in postsynaptic cerebellar Purkinje neurons, which have a high level of InsP(3) receptors(5). We find that repetitive activation of the synapse between parallel fibres and Purkinje cells causes InsP(3)-mediated Ca2+ release in the Purkinje cells. This Ca2+ release is restricted to individual postsynaptic spines, where both metabotropic glutamate receptors(6,7) and InsP3 receptors(5) are located, or to multiple spines and adjacent dendritic shafts. Focal photolysis of caged InsP(3) (ref. 8) in Purkinje cell dendrites also produces Ca2+ signals that spread only a few micrometres from the site of InsP(3) production. Uncaged InsP(3) produces a long-lasting depression of parallel-fibre synaptic transmission that is limited to synapses where the Ca2+ concentration is raised. Thus, in Purkinje cells InP3 acts within a restricted spatial range that allows it to regulate the function of local groups of parallel-fibre synapses.