NMDA receptor subunit-dependent [Ca2+] signaling in individual hippocampal dendritic spines
NMDA receptor subunit-dependent [Ca2+] signaling in individual hippocampal dendritic spines
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DOI：
10.1523/jneurosci.1221-05.2005
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发表时间：
2005-06-29
影响因子：
5.3
通讯作者：
Svoboda, K
中科院分区：
文献类型：
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作者：
Sobczyk, A;Scheuss, V;Svoboda, K
钙离子（Ca²⁺）通过突触N - 甲基 - D - 天冬氨酸受体（NMDA - Rs）内流会触发多种适应性细胞过程。为了探究NMDA - R介导的[Ca²⁺]信号传导，我们利用双光子谷氨酸解笼锁技术刺激大鼠脑切片中CA1锥体神经元单个树突棘上的NMDA - Rs。我们测量了胞体处的NMDA - R电流以及受刺激树突棘中NMDA - R介导的[Ca²⁺]瞬变（Δ[Ca²⁺]）。解笼锁诱发的NMDA - R电流幅度与受刺激树突棘的大小无关，这意味着较小的树突棘含有更高密度的功能性NMDA - Rs。在不同树突棘之间，Δ[Ca²⁺]与NMDA - R电流的比值变化很大（10倍的差异），尤其是对于小树突棘。这些差异无法用树突棘大小的异质性或树突棘与其母树突之间的扩散耦合来解释。此外，我们发现小树突棘的NMDA - R电流对NMDA - R的NR2B亚基特异性拮抗剂敏感。在阻断含NR2B的受体后，Δ[Ca²⁺]/NMDA - R电流比值的范围及其平均值大幅降低。我们的数据表明，单个树突棘能够调节其NMDA - Rs的亚基组成以及通过这些受体的有效钙离子分电流。
Ca2+ influx through synaptic NMDAreceptors (NMDA-Rs) triggers a variety of adaptive cellular processes. To probe NMDA-R-mediated [Ca2+] signaling, we used two-photon glutamate uncaging to stimulate NMDA- Rs on individual dendritic spines of CA1 pyramidal neurons in rat brain slices. We measured NMDA-R currents at the soma and NMDA-R- mediated [Ca2+] transients in stimulated spines (Delta[Ca2+]). Uncaging- evoked NMDA- R current amplitudes were independent of the size of the stimulated spine, implying that smaller spines contain higher densities of functional NMDA-Rs. The ratio of Delta[Ca2+] over NMDA- R current was highly variable ( factor of 10) across spines, especially for small spines. These differences were not explained by heterogeneity in spine sizes or diffusional coupling between spines and their parent dendrites. In addition, we find that small spines have NMDA-R currents that are sensitive to NMDA-R NR2B subunit-specific antagonists. With block of NR2B-containing receptors, the range of Delta[Ca2+]/NMDA-R current ratios and their average value were much reduced. Our data suggest that individual spines can regulate the subunit composition of their NMDA- Rs and the effective fractional Ca2+ current through these receptors.