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SK通道通过调节CaMKIIα/β动力学来调控突触可塑性。

SK Channel Modulates Synaptic Plasticity by Tuning CaMKIIα/β Dynamics.

作者信息

Shrestha Amita, Sultana Razia, Lee Charles C, Ogundele Olalekan M

机构信息

Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.

出版信息

Front Synaptic Neurosci. 2019 Oct 31;11:18. doi: 10.3389/fnsyn.2019.00018. eCollection 2019.

DOI:10.3389/fnsyn.2019.00018
PMID:31736736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6834780/
Abstract

N-Methyl-D-Aspartate Receptor 1 (NMDAR)-linked Ca current represents a significant percentage of post-synaptic transient that modulates synaptic strength and is pertinent to dendritic spine plasticity. In the hippocampus, Ca transient produced by glutamatergic ionotropic neurotransmission facilitates Ca-Calmodulin-dependent kinase 2 (CaMKII) Thr286 phosphorylation and promote long-term potentiation (LTP) expression. At CA1 post-synaptic densities, Ca transients equally activate small conductance (SK2) channel which regulates excitability by suppressing Ca movement. Here, we demonstrate that upstream attenuation of GluN1 function in the hippocampus led to a decrease in Thr286 CaMKIIα phosphorylation, and increased SK2 expression. Consistent with the loss of GluN1 function, potentiation of SK channel in wild type hippocampus reduced CaMKIIα expression and abrogate synaptic localization of T286 pCaMKIIα. Our results demonstrate that positive modulation of SK channel at hippocampal synapses likely refine GluN1-linked plasticity by tuning dendritic localization of CaMKIIα.

摘要

N-甲基-D-天冬氨酸受体1（NMDAR）相关的钙电流在突触后瞬变中占很大比例，可调节突触强度，并且与树突棘可塑性相关。在海马体中，谷氨酸能离子型神经传递产生的钙瞬变促进钙/钙调蛋白依赖性蛋白激酶2（CaMKII）苏氨酸286位点的磷酸化，并促进长时程增强（LTP）的表达。在CA1突触后致密区，钙瞬变同样会激活小电导（SK2）通道，该通道通过抑制钙移动来调节兴奋性。在此，我们证明海马体中GluN1功能的上游衰减导致苏氨酸286位点的CaMKIIα磷酸化减少，并增加了SK2的表达。与GluN1功能丧失一致，野生型海马体中SK通道的增强降低了CaMKIIα的表达，并消除了T286 pCaMKIIα的突触定位。我们的结果表明，海马体突触处SK通道的正向调节可能通过调整CaMKIIα的树突定位来优化GluN1相关的可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/686f923ef575/fnsyn-11-00018-g0014.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/2be2ec542c10/fnsyn-11-00018-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/00c33f8308e3/fnsyn-11-00018-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/bb8108be0d04/fnsyn-11-00018-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/1566e63cfd68/fnsyn-11-00018-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/426ec6f1bf90/fnsyn-11-00018-g0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/6902ee4dcbb4/fnsyn-11-00018-g0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/fb86592a0616/fnsyn-11-00018-g0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/686f923ef575/fnsyn-11-00018-g0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/7e365ac36c8d/fnsyn-11-00018-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/2c2ede7c8502/fnsyn-11-00018-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/4247f98dafe3/fnsyn-11-00018-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/a6fdc9220bcd/fnsyn-11-00018-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/ebe564d7836a/fnsyn-11-00018-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/6b2f55372273/fnsyn-11-00018-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/2be2ec542c10/fnsyn-11-00018-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/00c33f8308e3/fnsyn-11-00018-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/bb8108be0d04/fnsyn-11-00018-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/1566e63cfd68/fnsyn-11-00018-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/426ec6f1bf90/fnsyn-11-00018-g0011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/fb86592a0616/fnsyn-11-00018-g0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b9/6834780/686f923ef575/fnsyn-11-00018-g0014.jpg

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3
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4
An Association Study of DNA Methylation and Gene Expression in Angelman Syndrome: A Bioinformatics Approach.《Angelman 综合征的 DNA 甲基化和基因表达的关联研究：一种生物信息学方法》
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5
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6
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7
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5
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8
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J Neurosci. 2017 Nov 1;37(44):10690-10699. doi: 10.1523/JNEUROSCI.2141-17.2017. Epub 2017 Oct 2.
10
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Plant Signal Behav. 2017 Jul 3;12(7):e1343779. doi: 10.1080/15592324.2017.1343779.