A CaV2.1 calcium channel mutation rocker reduces the number of postsynaptic AMPA receptors in parallel fiber-Purkinje cell synapses
A CaV2.1 calcium channel mutation rocker reduces the number of postsynaptic AMPA receptors in parallel fiber-Purkinje cell synapses
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DOI：
10.1111/j.1460-9568.2006.05191.x
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发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
Imoto, Keiji
中科院分区：
文献类型：
--
作者：
Kodama, Takashi;Itsukaichi-Nishida, Yuko;Imoto, Keiji
rocker小鼠是遗传性共济失调突变体，其在编码Ca（V）2.1（P/Q型）Ca 2+通道α（1）亚基的基因中携带点突变，并且在报道的Ca（V）2.1突变小鼠中表现出最轻微的症状。我们研究了摇杆突变型钙通道的基本特性及其对小脑浦肯野细胞（PC）兴奋性突触传递的影响。在急性分离的PC胞体中，摇杆突变体通道显示Ca 2+通道电流密度中度降低，而其动力学和门控电压依赖性保持接近正常。尽管通道功能发生了微小变化，但平行纤维（PF）-PC突触中的突触传递严重受损。对PC的攀爬纤维输入表现出中度损伤，但可以引起正常的复杂尖峰。突触前功能的PF-PC突触，然而，出乎意料的是几乎正常的成对脉冲促进，敏感性细胞外Ca 2+浓度和谷氨酸浓度的突触裂缝。包括冷冻断裂复制标记在内的电子显微镜分析显示，突触后α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体的数量和密度均大幅减少，而PF-PC突触的总体结构没有变化。我们还观察到一个异常的树枝状的PC树突在年轻的成年摇杆小鼠（类似于1个月大）。这些证据表明，即使是Ca（V）2.1 Ca ~（2+）通道的中度功能障碍也能引起PF-PC突触后分子组成和PC树突结构的显著变化。
The rocker mice are hereditary ataxic mutants that carry a point mutation in the gene encoding the Ca(V)2.1 (P/Q-type) Ca2+ channel alpha(1) subunit, and show the mildest symptoms among the reported Ca(V)2.1 mutant mice. We studied the basic characteristics of the rocker mutant Ca2+ channel and their impacts on excitatory synaptic transmission in cerebellar Purkinje cells (PCs). In acutely dissociated PC somas, the rocker mutant channel showed a moderate reduction in Ca2+ channel current density, whereas its kinetics and voltage dependency of gating remained nearly normal. Despite the small changes in channel function, synaptic transmission in the parallel fiber (PF)-PC synapses was severely impaired. The climbing fiber inputs onto PCs showed a moderate impairment but could elicit normal complex spikes. Presynaptic function of the PF-PC synapses, however, was unexpectedly almost normal in terms of paired-pulse facilitation, sensitivity to extracellular Ca2+ concentration and glutamate concentration in synaptic clefts. Electron microscopic analyses including freeze-fracture replica labeling revealed that both the number and density of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors substantially decreased without gross structural changes of the PF-PC synapses. We also observed an abnormal arborization of PC dendrites in young adult rocker mice (similar to 1 month old). These lines of evidence suggest that even a moderate dysfunction of Ca(V)2.1 Ca2+ channel can cause substantial changes in postsynaptic molecular composition of the PF-PC synapses and dendritic structure of PCs.