Decrease in calbindin content significantly alters LTP but not NMDA receptor and calcium channel properties
Decrease in calbindin content significantly alters LTP but not NMDA receptor and calcium channel properties
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DOI：
10.1016/s0028-3908(01)00202-7
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发表时间：
2002-03-01
影响因子：
4.7
通讯作者：
Billard, JM
中科院分区：
文献类型：
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作者：
Jouvenceau, A;Potier, B;Billard, JM
在野生型和反义转基因 CaBP 缺陷小鼠的海马 CA I 区域中研究了胞质钙结合蛋白 D-28K (CaBP) 对突触可塑性的贡献。我们发现，CaBP 缺陷小鼠中强直刺激诱导的长时程增强 (LTP) 受到损害。 CaBP 缺陷小鼠中 NMDA 受体的基本生物物理特性及其数量没有改变。我们还证明了钙通道的生理特性在基因型之间是相同的。通过 NMDA 受体或钙通道的 Ca2+ 进入不足。或 NMDA 受体密度的降低不太可能解释 LTP 的这种损害。有趣的是，我们发现甘氨酸不能阻止 LTP 的损失，但在低浓度 NMDA 受体拮抗剂 D-APV（5 μM）和钙螯合剂 BAPTA-AM（5 μM）存在下可以恢复 LTP 的损失。此外，我们观察到当突触后破伤风诱导的 [Ca2+](i) 升高过度增加时，野生型小鼠的 LTP 会丧失。相反，较弱的破伤风刺激可以在 CaBP 缺陷小鼠中诱导和维持 LTP。这些结果表明，由于 CaBP 表达减少，细胞质 [Ca2+](i) 升高可能会损害 LTP 诱导和维持机制，而不影响钙进入机制。因此。 CaBP 通过将细胞质中钙的升高限制在适当的时空模式中，在 Iona 期突触可塑性中发挥关键作用。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
The contribution of the cytosolic Calcium binding protein calbindin D-28K (CaBP) to the synaptic plasticity was investigated in hippocampal CA I area of wild-type and antisense transgenic CaBP-deficient mice. We showed that long-term potentiation (LTP) induced by tetanic stimulation in CaBP-deficient mice was impaired. The fundamental biophysical properties of NMDA receptors and their number were not modified in CaBP-deficient mice. We also demonstrated that the physiological properties of calcium channels were identical between genotypes. An insufficient Ca2+ entry through NMDA receptors Or calcium channels. or a decrease in NMDA receptor density are unlikely to explain this impairment of LTP. Interestingly, we showed that the loss of LTP was not prevented by glycine but was restored in the presence of a low concentration of the NMDA receptor antagonist D-APV (5 muM) and of the calcium chelator BAPTA-AM (5 muM). Moreover, we observed it loss of LTP in the wild-type mice when the postsynaptic tetanic-induced [Ca2+](i) rise is excessively increased. Conversely, a weaker tetanus stimulation allowed LTP induction and maintenance in CaBP-deficient mice. These results suggest that a higher cytosol [Ca2+](i), due to the decrease of CaBP expression may impair LTP induction and maintenance mechanisms without affecting the mechanisms of calcium entry. Thus. CaBP plays a critical role in Iona term synaptic plasticity by limiting the elevation of calcium rise in the cytosol to sonic appropriate spatio-temporal pattern. (C) 2002 Elsevier Science Ltd. All rights reserved.