Nusser Z, Sieghart W, Stephenson F A, Somogyi P
Medical Research Council, Anatomical Neuropharmacology Unit, University of Oxford, United Kingdom.
J Neurosci. 1996 Jan;16(1):103-14. doi: 10.1523/JNEUROSCI.16-01-00103.1996.
Although three distinct subunits seem to be sufficient to form a functional pentameric GABAA receptor channel, cerebellar granule cells express nRNA for nine subunits. They receive GABAergic input from a relatively homogenous population of Golgi cells. It is not known whether all subunits are distributed similarly on the surface of granule cells or whether some of them have differential subcellular distribution resulting in distinct types of synaptic and/or extrasynaptic channels. Antibodies to different parts of the alpha 6 and alpha 1 subunits of the GABAA receptor and electron microscopic immunogold localization were used to determine the precise subcellular distribution of these subunits in relation to specific synaptic inputs. Both subunits were present in the extrasynaptic dendritic and somatic membranes at lower densities than in synaptic junctions. The alpha 6 and alpha 1 subunits were colocalized in many GABAergic Golgi synapses, demonstrating that both subunits are involved in synaptic transmission in the same synapse. Synapses immunopositive for only one of the alpha subunits were also found. The alpha 6, but not the alpha 1, subunit was also concentrated in glutamatergic mossy fiber synapses, indicating that the alpha 6 subunit may have several roles depending on its different locations. The results demonstrate a partially differential synaptic targeting of two distinct GABAA receptor subunits on the surface of the same type of neuron.
虽然三个不同的亚基似乎足以形成一个功能性的五聚体GABAA受体通道，但小脑颗粒细胞表达9种亚基的nRNA。它们从相对同质的高尔基细胞群体接收GABA能输入。目前尚不清楚所有亚基在颗粒细胞表面的分布是否相似，或者其中一些亚基是否具有不同的亚细胞分布，从而导致不同类型的突触和/或突触外通道。使用针对GABAA受体α6和α1亚基不同部分的抗体以及电子显微镜免疫金定位来确定这些亚基相对于特定突触输入的精确亚细胞分布。两个亚基在突触外树突和体细胞膜中的密度均低于突触连接处。α6和α1亚基在许多GABA能高尔基突触中共定位，表明这两个亚基都参与同一突触中的突触传递。还发现了仅对其中一种α亚基呈免疫阳性的突触。α6亚基而非α1亚基也集中在谷氨酸能苔藓纤维突触中，这表明α6亚基可能因其不同位置而具有多种作用。结果表明，在同一类型神经元表面，两种不同的GABAA受体亚基存在部分差异的突触靶向作用。
