Finch E A, Augustine G J
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nature. 1998;396(6713):753-6. doi: 10.1038/25541.
The second messenger inositol-1,4,5-trisphosphate (InsP3) releases Ca2+ from intracellular Ca2+ stores by activating specific receptors on the membranes of these stores. In many cells, InsP3 is a global signalling molecule that liberates Ca2+ throughout the cytoplasm. However, in neurons the situation might be different, because synaptic activity may produce InsP3 at discrete locations. Here we characterize InsP3 signalling in postsynaptic cerebellar Purkinje neurons, which have a high level of InsP3 receptors. We find that repetitive activation of the synapse between parallel fibres and Purkinje cells causes InsP3-mediated Ca2+ release in the Purkinje cells. This Ca2+ release is restricted to individual postsynaptic spines, where both metabotropic glutamate receptors and InsP3 receptors are located, or to multiple spines and adjacent dendritic shafts. Focal photolysis of caged InsP3 in Purkinje cell dendrites also produces Ca2+ signals that spread only a few micrometres from the site of InsP3 production. Uncaged InsP3 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.
第二信使肌醇 -1,4,5 -三磷酸（InsP3）通过激活细胞内钙库膜上的特定受体，从细胞内钙库释放Ca2+。在许多细胞中，InsP3是一种全局信号分子，可在整个细胞质中释放Ca2+。然而，在神经元中情况可能有所不同，因为突触活动可能在离散位置产生InsP3。在这里，我们描述了突触后小脑浦肯野神经元中的InsP3信号传导，这些神经元具有高水平的InsP3受体。我们发现，平行纤维与浦肯野细胞之间突触的重复激活会导致浦肯野细胞中InsP3介导的Ca2+释放。这种Ca2+释放局限于单个突触后棘，代谢型谷氨酸受体和InsP3受体都位于此处，或者局限于多个棘和相邻的树突轴。对浦肯野细胞树突中笼锁InsP3进行局部光解也会产生Ca2+信号，这些信号仅从InsP3产生的位点扩散几微米。释放的InsP3会导致平行纤维突触传递产生持久抑制，这种抑制仅限于Ca2+浓度升高的突触。因此，在浦肯野细胞中，InsP3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群的功能。
