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钾离子通道改善耳蜗核中听觉神经元的时间处理能力。

Kv channels improve the temporal processing of auditory neurons in the cochlear nucleus.

作者信息

Zhang Chuangeng, Wang Meijian, Zhang Tingting, Xie Ruili

机构信息

Department of Otolaryngology - Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Department of Neuroscience, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

出版信息

J Physiol. 2024 Dec 4. doi: 10.1113/JP286174.

Abstract

Kv channels generate A-type current known to regulate neuronal excitability. Its role in processing timing information is understudied, especially in the auditory system where temporal information is crucial for hearing. In the cochlear nucleus, principal bushy neurons are specialized for temporal processing with distinct biophysical properties owing to their expression of various voltage-gated ion channels. Previous studies reported conflicting information regarding the expression and potential role of Kv channels in these neurons. We explored these questions using electrophysiology in CBA/CaJ mice of either sex. A-type current was isolated from 88% of bushy neurons using Kv channel-selective blocker Jingzhaotoxin-X (JZ-X), which increased the intrinsic excitability of bushy neurons without altering their synaptic input. During high-rate activity, JZ-X treatment significantly increased the spike jitter and reduced the firing threshold of bushy neurons. In old mice, A-type current in bushy neurons reduced in magnitude but maintained current density, accompanied by decreased membrane surface area. In contrast, TEA-sensitive Kv current reduced in both magnitude and current density, indicative of a greater contribution to the altered biophysical properties of bushy neurons during ageing. Our findings suggest that Kv channels play significant roles in regulating neuronal excitability and improving the temporal processing of bushy neurons. Such function is likely retained with age and is not the primary mechanism driving compromised temporal processing under age-related hearing loss. KEY POINTS: Most bushy neurons of the cochlear nucleus exhibit Kv-mediated A-type current. A-type current regulates neuronal excitability of bushy neurons without contributing to the synaptic transmission at the endbulb of Held. A-type current increases the firing threshold and improves the temporal precision of spikes in bushy neurons during high-rate activity. A-type current reduces peak amplitude in bushy neurons during ageing but maintains current density. Decreased Kv current, rather than Kv current, likely play more significant roles in altering the biophysical properties of bushy neurons during ageing, contributing to compromised temporal processing during age-related hearing loss.

摘要

钾离子通道产生已知可调节神经元兴奋性的A 型电流。其在处理时间信息方面的作用尚未得到充分研究,尤其是在听觉系统中,时间信息对听力至关重要。在耳蜗核中,主要的浓密神经元专门用于时间处理,由于它们表达各种电压门控离子通道,具有独特的生物物理特性。先前的研究报告了关于钾离子通道在这些神经元中的表达和潜在作用的相互矛盾的信息。我们使用电生理学方法在不同性别的CBA/CaJ小鼠中探索了这些问题。使用钾离子通道选择性阻滞剂京蝎毒素-X(JZ-X)从88%的浓密神经元中分离出A 型电流,这增加了浓密神经元的内在兴奋性,而不改变其突触输入。在高速率活动期间,JZ-X处理显著增加了浓密神经元的峰电位抖动并降低了其放电阈值。在老年小鼠中,浓密神经元中的A 型电流幅度减小但电流密度保持不变,同时膜表面积减小。相比之下,四乙铵敏感的钾离子电流在幅度和电流密度上均减小,表明其在衰老过程中对浓密神经元生物物理特性改变的贡献更大。我们的研究结果表明,钾离子通道在调节神经元兴奋性和改善浓密神经元的时间处理方面发挥着重要作用。这种功能可能随着年龄的增长而保留,并且不是导致与年龄相关的听力损失时时间处理受损的主要机制。要点:耳蜗核的大多数浓密神经元表现出钾离子介导的A 型电流。A 型电流调节浓密神经元的神经元兴奋性,但对赫尔德终球处的突触传递没有贡献。在高速率活动期间,A 型电流增加浓密神经元的放电阈值并提高峰电位的时间精度。在衰老过程中,A 型电流在浓密神经元中的峰值幅度减小但电流密度保持不变。钾离子电流的减少,而非A 型电流,可能在衰老过程中改变浓密神经元生物物理特性方面发挥更重要的作用,导致与年龄相关的听力损失时时间处理受损。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03c2/12559986/7f7f5981c4e7/TJP-603-6285-g007.jpg

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