Protection from Noise-Induced Hearing Loss by Kv2.2 Potassium Currents in the Central Medial Olivocochlear System
Protection from Noise-Induced Hearing Loss by Kv2.2 Potassium Currents in the Central Medial Olivocochlear System
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DOI：
10.1523/jneurosci.5043-12.2013
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发表时间：
2013-05-22
影响因子：
5.3
通讯作者：
Forsythe, Ian D.
中科院分区：
文献类型：
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作者：
Tong, Huaxia;Kopp-Scheinpflug, Cornelia;Forsythe, Ian D.
中央听觉脑干提供被称为内侧橄榄耳蜗（MOC）系统的传出投射，其调节耳蜗放大器并介导对暴露于响亮声音的保护。它起源于斜方体腹侧核（VNTB）的神经元，因此控制该通路中的神经元兴奋性对听力有深远的影响。VNTB和斜方体内侧核是Kv2.2电压门控钾通道在听性脑干中表达的唯一位点，与这些通道的专门功能一致。在没有明确拮抗剂的情况下，我们使用重组和转基因方法来研究Kv2.2如何促进MOC传出功能。在野生型小鼠中显性负性Kv2.2的病毒基因转移抑制外向K+电流，增加动作电位（AP）半宽并减少重复放电。类似地，来自Kv2.2敲除小鼠（Kv2.2KO）的VNTB神经元也显示出增加的AP持续时间。对照实验确定Kv2.2在耳蜗中不表达，因此Kv2.2KO小鼠中听觉功能的任何变化必须是中枢起源。此外，听觉脑干反应的体内记录显示，这些Kv2.2KO小鼠更容易受到噪声诱导的听力损失。我们的结论是，Kv2.2调节神经元的兴奋性，在这些脑干核团维持短AP和增强高频放电。这在高强度声音期间保护传出MOC放电，并且在听觉过度刺激后的保护调解中至关重要。
The central auditory brainstem provides an efferent projection known as the medial olivocochlear (MOC) system, which regulates the cochlear amplifier and mediates protection on exposure to loud sound. It arises from neurons of the ventral nucleus of the trapezoid body (VNTB), so control of neuronal excitability in this pathway has profound effects on hearing. The VNTB and the medial nucleus of the trapezoid body are the only sites of expression for the Kv2.2 voltage-gated potassium channel in the auditory brainstem, consistent with a specialized function of these channels. In the absence of unambiguous antagonists, we used recombinant and transgenic methods to examine how Kv2.2 contributes to MOC efferent function. Viral gene transfer of dominant-negative Kv2.2 in wild-type mice suppressed outward K+ currents, increasing action potential (AP) half-width and reducing repetitive firing. Similarly, VNTB neurons from Kv2.2 knock-out mice (Kv2.2KO) also showed increased AP duration. Control experiments established that Kv2.2 was not expressed in the cochlea, so any changes in auditory function in the Kv2.2KO mouse must be of central origin. Further, in vivo recordings of auditory brainstem responses revealed that these Kv2.2KO mice were more susceptible to noise-induced hearing loss. We conclude that Kv2.2 regulates neuronal excitability in these brainstem nuclei by maintaining short APs and enhancing high-frequency firing. This safeguards efferent MOC firing during high-intensity sounds and is crucial in the mediation of protection after auditory overexposure.