Basket to Purkinje Cell Inhibitory Ephaptic Coupling Is Abolished in Episodic Ataxia Type 1.
Basket to Purkinje Cell Inhibitory Ephaptic Coupling Is Abolished in Episodic Ataxia Type 1.
复制标题
在1型的情节性共济失调中，废除了purkinje细胞抑制作用的抑制作用偶联。
DOI：
10.3390/cells12101382
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发表时间：
2023-05-13
期刊：
影响因子：
6
通讯作者：
Kullmann, Dimitri M.
中科院分区：
文献类型：
--
作者：
Martin, Henry G. S.;Kullmann, Dimitri M.
编码KV1.1钾通道亚基的KCNA1基因的显性遗传错义突变导致1型发作性共济失调（EA1）。虽然小脑不协调被认为是由异常浦肯野细胞输出引起的，但潜在的功能缺陷尚不清楚。在此，我们研究了成年小鼠EA1模型中小脑篮细胞对浦肯野细胞的突触和非突触抑制作用。篮状细胞末端的突触功能不受影响，尽管它们对含有kv1.1的通道有强烈的富集。反过来，量化篮细胞输入对Purkine细胞输出影响的相响应曲线得以维持。然而，与野生型小鼠相比，EA1小鼠在浦肯野细胞轴突初始段周围的小脑“针状”形成中发生的超快速非突触性偶合明显减少。篮子细胞抑制浦肯野细胞的时间谱的改变强调了Kv1.1通道对这种信号传导形式的重要性，并可能有助于EA1的临床表型。
Dominantly inherited missense mutations of the KCNA1 gene, which encodes the KV1.1 potassium channel subunit, cause Episodic Ataxia type 1 (EA1). Although the cerebellar incoordination is thought to arise from abnormal Purkinje cell output, the underlying functional deficit remains unclear. Here we examine synaptic and non-synaptic inhibition of Purkinje cells by cerebellar basket cells in an adult mouse model of EA1. The synaptic function of basket cell terminals was unaffected, despite their intense enrichment for KV1.1-containing channels. In turn, the phase response curve quantifying the influence of basket cell input on Purkine cell output was maintained. However, ultra-fast non-synaptic ephaptic coupling, which occurs in the cerebellar ‘pinceau’ formation surrounding the axon initial segment of Purkinje cells, was profoundly reduced in EA1 mice in comparison with their wild type littermates. The altered temporal profile of basket cell inhibition of Purkinje cells underlines the importance of Kv1.1 channels for this form of signalling, and may contribute to the clinical phenotype of EA1.
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影响因子：
16.6
作者：
Begum R;Bakiri Y;Volynski KE;Kullmann DM
通讯作者：
Kullmann DM
影响因子：
25
作者：
Han KS;Chen CH;Khan MM;Guo C;Regehr WG
通讯作者：
Regehr WG
影响因子：
16.2
作者：
Adelman, JP;Bond, CT;Maylie, J
通讯作者：
Maylie, J
影响因子：
2.5
作者：
Connor, JX;McCormack, K;Messing, A
通讯作者：
Messing, A
DOI：
10.1016/s0169-328x(96)00120-9
发表时间：
1996-11-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Laube, G;Roper, J;Veh, RW
通讯作者：
Veh, RW