L-type calcium channels in the auditory system
L-type calcium channels in the auditory system
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听觉系统中的 L 型钙通道
DOI：
10.1007/s13295-014-0059-3
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Friauf E
中科院分区：
文献类型：
--
作者：
Nothwang HG;Engel J;Knipper M;Friauf E
电压激活的L-型钙通道Cav1.2和Cav1.3介导Ca ~（2+）内流进入索马或树突的神经元，而在突触前没有观察到。令人惊讶的是，在内耳中，Cav1.3对于从突触前耳蜗内毛细胞到突触后听觉神经纤维的信号传输是不可或缺的。由于Cav1.3通道在条带处聚集，即，作为毛细胞的特定突触前结构，它们促进Ca 2+内流，这触发突触囊泡与质膜的钙依赖性融合。编码Cav1.3的基因Cacna 1d的突变会导致耳聋，因为突触处神经递质谷氨酸的释放被取消。此外，听觉通路的研究表明Cav1.3在中枢听觉系统中也起着重要作用。该通道的缺失导致听觉通路细胞结构的严重变化和听觉神经元的异常电生理表现。此外，发育完善的tonotopic抑制性预测的声音定位电路被破坏。这些畸变与听觉通路中的异常声音处理有关。这表明Cav1.3通道对于内耳功能以及听觉通路的发育和表现是必不可少的。因此，Cacna 1d代表了一个原型的肥胖相关基因，其中突变导致外周和中枢听觉缺陷。这反过来又对使用人工耳蜗进行听觉康复产生了影响，人工耳蜗只能解决外周功能障碍。对密切相关的Cav1.2亚型的探索性研究指出了该通道在声损伤中的重要作用。Cav1.2主要在听神经中表达，但显然不是正常听觉功能所必需的。然而，通道功能的丧失确实会影响创伤性噪声暴露的效果。与对照组相比，噪声损伤引起的这一通道的丧失导致听阈增加降低。这一现象表明Cav1.2介导的Ca 2+内流参与了噪声创伤引起的损伤。更深入地了解这一功能可能会导致新的治疗方法。
The voltage-activated L-type calcium channels Cav1.2 and Cav1.3 mediate Ca2+influx into neurons at the soma or at dendrites, whereas they are not observed at the presynapse. Surprisingly, in the inner ear, Cav1.3 is indispensable for signal transmission from the presynaptic cochlear inner hair cells to the postsynaptic auditory nerve fibers. Due to Cav1.3 channel clustering at ribbons, i.e., specific presynaptic structures of the hair cells, they promote Ca2+influx, which triggers calcium-dependent fusion of synaptic vesicles with the plasma membrane. Mutations inCacna1d, a gene that encodes Cav1.3, result in deafness because release of the neurotransmitter glutamate at the synapses is abolished. Moreover, studies of the auditory pathway have revealed that Cav1.3 plays an important part in the central auditory system as well. Absence of the channel results in severe changes in auditory pathway cytoarchitecture and in abnormal electrophysiological performance of auditory neurons. Furthermore, developmental refinement of tonotopic inhibitory projections in sound localization circuits is disrupted. These aberrations are associated with abnormal sound processing in the auditory pathway. This goes to show that the Cav1.3 channel is essential for inner ear functioning as well as auditory pathway development and performance.Cacna1dtherefore represents a prototypal deafness-associated gene, in which mutations result in both peripheral and central auditory deficiencies. This, in turn, has implications for auditory rehabilitation using cochlear implants that address only peripheral dysfunctions. Exploratory research into the closely related Cav1.2 isoform points to an important role of this channel in acoustic trauma. Cav1.2 is mainly expressed in the auditory nerve, but apparently not essential for normal auditory function. Loss of function of the channel, however, does influence the effects of traumatic noise exposure. Loss of this channel induced by noise trauma results in reduced auditory threshold increase—as compared with the control group. This phenomenon points to the fact that Cav1.2-mediated Ca2+influx is involved in noise trauma-induced damage. Deeper insight into this function might result in new therapeutic approaches.
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