Saber Mahshid Helia, Kaiser Michaela, Rüttiger Lukas, Körber Christoph
Department of Functional Neuroanatomy, Institute of Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
Front Cell Neurosci. 2024 Nov 1;18:1463816. doi: 10.3389/fncel.2024.1463816. eCollection 2024.
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.
听觉信号的处理严重依赖于神经元在高频下长时间精确地发放短暂动作电位（AP）的能力以及高保真度。这需要表达特定的离子通道组，以使神经元快速复极化，防止异常的AP发放，并严格调节神经元的兴奋性。尽管至关重要，但在听觉系统中，神经元兴奋性的调节却很少受到关注。神经元兴奋性在很大程度上由静息膜电位（RMP）决定，而静息膜电位又取决于静息时开放的离子通道的种类和数量，主要是钾通道。这种静息钾电导的很大一部分由双孔钾通道（K2P通道）介导。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中具有特殊作用。然而，由于它在异源表达系统中未能形成功能性离子通道，因此长期以来被归类为“无功能”，其在听觉系统中的作用仍然难以捉摸。在此，我们培育了Task5基因敲除（KO）小鼠。Task5的缺失导致了腹侧耳蜗核（VCN）的毛细胞和梯形体内侧核（MNTB）的主要神经元的神经元兴奋性发生变化。此外，Tasko5-KO小鼠对大声的听觉脑干反应（ABR）也发生了改变。因此，我们的研究提供了证据，证明Task5确实是一个功能性的K2P亚基，并有助于听觉脑干中的声音处理。
