Channelopathies and dendritic dysfunction in fragile X syndrome.
Channelopathies and dendritic dysfunction in fragile X syndrome.
复制标题
脆性 X 综合征中的通道病和树突功能障碍。
DOI：
10.1016/j.brainresbull.2014.01.002
复制
发表时间：
2014-04
影响因子：
3.8
通讯作者：
Johnston D
中科院分区：
文献类型：
--
作者：
Brager DH;Johnston D
树突棘异常和代谢型谷氨酸受体理论将焦点直接放在突触和蛋白质合成作为脆性X综合征的细胞位点上。然而，突触只是部分负责神经元网络中的信息处理。神经递质触发的兴奋性突触后电位（EPSP）是由树突状电压门控离子通道形成和整合的。这些EPSP，以及在某些情况下产生的树突棘波，在它们传播到索马时被树突电压门控离子通道进一步修饰。如果所产生的体细胞去极化足够大，则动作电位将被触发并沿轴突顺向传播，在轴突中它可以触发神经递质释放，并且逆向传播回到树突树中，在树突树中它可以激活和修饰树突电压门控和受体激活的离子通道。在脆性X综合征的fmr 1-/y小鼠模型中鉴定了几种通道病，包括体细胞-树突（L-型钙通道、松弛钾通道、h-通道、A-型钾通道）和轴-体细胞（BK通道和延迟整流钾通道）。这些通道的病理功能将强烈影响单个神经元的兴奋性以及整体网络功能。在这一章中，我们讨论了电压门控离子通道在神经元处理中的作用，并描述了如何确定在脆性X综合征的模型channelopathies可能在树突状病理生理学中发挥作用。
Dendritic spine abnormalities and the metabotropic glutamate receptor theory put the focus squarely on synapses and protein synthesis as the cellular locus of Fragile X syndrome. Synapses however, are only partly responsible for information processing in neuronal networks. Neurotransmitter triggered excitatory postsynaptic potentials (EPSPs) are shaped and integrated by dendritic voltage-gated ion channels. These EPSPs, and in some cases the resultant dendritic spikes, are further modified by dendritic voltage-gated ion channels as they propagate to the soma. If the resultant somatic depolarization is large enough, action potential(s) will be triggered and propagate both orthodromically down the axon, where it may trigger neurotransmitter release, and antidromically back into the dendritic tree, where it can activate and modify dendritic voltage-gated and receptor activated ion channels. Several channelopathies, both soma-dendritic (L-type calcium channels, Slack potassium channels, h-channels, A-type potassium channels) and axo-somatic (BK channels and delayed rectifier potassium channels) were identified in the fmr1-/y mouse model of Fragile X syndrome. Pathological function of these channels will strongly influence the excitability of individual neurons as well as overall network function. In this chapter we discuss the role of voltage-gated ion channels in neuronal processing and describe how identified channelopathies in models of Fragile X syndrome may play a role in dendritic pathophysiology.
登录
查看更多内容
影响因子：
4.8
作者：
Brenner, R;Jegla, TJ;Aldrich, RW
通讯作者：
Aldrich, RW
影响因子：
5.3
作者：
Campanac, Emilie;Daoudal, Gael;Debanne, Dominique
通讯作者：
Debanne, Dominique
影响因子：
16.2
作者：
Deng PY;Rotman Z;Blundon JA;Cho Y;Cui J;Cavalli V;Zakharenko SS;Klyachko VA
通讯作者：
Klyachko VA
影响因子：
3.7
作者：
Bittner, Katie C.;Andrasfalvy, Bertalan K.;Magee, Jeffrey C.
通讯作者：
Magee, Jeffrey C.
影响因子：
11.8
作者：
Dictenberg, Jason B.;Swanger, Sharon A.;Bassell, Gary J.
通讯作者：
Bassell, Gary J.