Kv1 potassium channels control action potential firing of putative GABAergic deep cerebellar nuclear neurons
Kv1 potassium channels control action potential firing of putative GABAergic deep cerebellar nuclear neurons
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DOI：
10.1038/s41598-020-63583-7
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发表时间：
2020-04-24
影响因子：
4.6
通讯作者：
Pedroarena, Christine M.
中科院分区：
文献类型：
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作者：
Pliego, Jessica Abigail Feria;Pedroarena, Christine M.
低阈电压激活的Kv 1钾通道在调节动作电位阈值、神经兴奋性和突触传递等方面起着重要作用。Kv 1通道在小脑中高度表达，人类Kv 1基因突变与间歇性共济失调（EAT-1）相关。除了Kv 1通道在控制小脑篮-浦肯野细胞突触中的公认作用外，Kv 1通道还由小脑深部核神经元（DCN）表达，在那里它们调节携带小脑输出的主要DCN的活性。DCN还包括具有重要功能的GABA能神经元，例如形成抑制性核橄榄通路的神经元、向小脑皮质提供反馈抑制的核皮质DCN以及靶向主要DCN的神经元，但其功能是否受Kv 1通道调节仍不清楚。在这里，使用成熟GAD 67-GFP小鼠的小脑切片来鉴定假定的GABA能-DCN（GAD+DCN），我们表明特异性Kv 1通道阻断剂（树突状毒素-α/I/K，DTXs）使躯体动作电位阈值超极化，增加自发放电率并阻碍GAD + DCN诱发的高频重复反应。此外，DTXs诱导躯体去极化和紧张性放电在以前沉默，假定的核皮质DCN。这些结果揭示了Kv 1通道在调节GABA能-DCN活性中的新作用，从而在多个水平上调节小脑功能。
Low threshold voltage activated Kv1 potassium channels play key roles in regulating action potential (AP) threshold, neural excitability, and synaptic transmission. Kv1 channels are highly expressed in the cerebellum and mutations of human Kv1 genes are associated to episodic forms of ataxia (EAT-1). Besides the well-established role of Kv1 channels in controlling the cerebellar basket-Purkinje cells synapses, Kv1 channels are expressed by the deep cerebellar nuclear neurons (DCNs) where they regulate the activity of principal DCNs carrying the cerebellar output. DCNs include as well GABAergic neurons serving important functions, such as those forming the inhibitory nucleo-olivary pathway, the nucleo-cortical DCNs providing feed-back inhibition to the cerebellar cortex, and those targeting principal DCNs, but whether their function is regulated by Kv1 channels remains unclear. Here, using cerebellar slices from mature GAD67-GFP mice to identify putative GABAergic-DCNs (GAD+DCN) we show that specific Kv1 channel blockers (dendrotoxin-alpha/I/K, DTXs) hyperpolarized the threshold of somatic action potentials, increased the spontaneous firing rate and hampered evoked high frequency repetitive responses of GAD + DCNs. Moreover, DTXs induced somatic depolarization and tonic firing in previously silent, putative nucleo-cortical DCNs. These results reveal a novel role of Kv1 channels in regulating GABAergic-DCNs activity and thereby, cerebellar function at multiple levels.