双孔钾通道亚基 Task5 对听觉脑干神经元功能和信号处理的影响

IF 4.2 3区 医学 Q2 NEUROSCIENCES Frontiers in Cellular Neuroscience Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI:10.3389/fncel.2024.1463816
Mahshid Helia Saber, Michaela Kaiser, Lukas Rüttiger, Christoph Körber
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引用次数: 0

摘要

听觉信号的处理严重依赖于神经元以高频率和高保真长时间发射短暂、精确定时的动作电位(AP)的能力。这就需要表达专门的离子通道,以快速使神经元恢复极化,防止异常的动作电位发射,并严格调节神经元的兴奋性。尽管神经元兴奋性的调节至关重要,但在听觉系统中却很少受到关注。神经元的兴奋性在很大程度上取决于静息膜电位(RMP),而静息膜电位又取决于静息时开放的离子通道(主要是钾通道)的种类和数量。静息钾传导的很大一部分是由双孔钾通道(K2P 通道)传导的。在 K2P 通道中,亚基 Task5 几乎只在听觉脑干中表达,这表明它在听觉处理过程中发挥着特殊作用。然而,由于它未能在异源表达系统中形成功能性离子通道,因此长期以来被归类为 "非功能性",其在听觉系统中的作用也一直难以捉摸。在这里,我们产生了Task5基因敲除(KO)小鼠。Task5缺失会导致腹侧耳蜗核(VCN)丛状细胞和梯形体内侧核(MNTB)主神经元的神经元兴奋性发生变化。此外,Tasko5-KO 小鼠对响声的听性脑干反应(ABRs)也发生了改变。因此,我们的研究为Task5确实是一种功能性K2P亚基并有助于听觉脑干的声音处理提供了证据。
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Effects of the two-pore potassium channel subunit Task5 on neuronal function and signal processing in the auditory brainstem.

Processing of auditory signals critically depends on the neuron's ability to fire brief, precisely timed action potentials (APs) at high frequencies and high fidelity for prolonged times. This requires the expression of specialized sets of ion channels to quickly repolarize neurons, prevent aberrant AP firing and tightly regulate neuronal excitability. Although critically important, the regulation of neuronal excitability has received little attention in the auditory system. Neuronal excitability is determined to a large extent by the resting membrane potential (RMP), which in turn depends on the kind and number of ion channels open at rest; mostly potassium channels. A large part of this resting potassium conductance is carried by two-pore potassium channels (K2P channels). Among the K2P channels, the subunit Task5 is expressed almost exclusively in the auditory brainstem, suggesting a specialized role in auditory processing. However, since it failed to form functional ion channels in heterologous expression systems, it was classified "non-functional" for a long time and its role in the auditory system remained elusive. Here, we generated Task5 knock-out (KO) mice. The loss of Task5 resulted in changes in neuronal excitability in bushy cells of the ventral cochlear nucleus (VCN) and principal neurons of the medial nucleus of the trapezoid body (MNTB). Moreover, auditory brainstem responses (ABRs) to loud sounds were altered in Tasko5-KO mice. Thus, our study provides evidence that Task5 is indeed a functional K2P subunit and contributes to sound processing in the auditory brainstem.

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来源期刊
CiteScore
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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