耳蜗内毛细胞中带状突触相关钙离子通道的研究进展  

Advances in Research on Ribbon Synaptic-Related Calcium Channels in Cochlear Inner Hair Cells

作　　者：范历强 陈正侬[1] FAN Liqiang;CHEN Zhengnong(Department of Otolaryngology Head and Neck Surgery,Shanghai Jiao Tong University Affiliated Shanghai Sixth People’s Hospital,Shanghai,200233)

机构地区：[1]上海交通大学附属第六人民医院耳鼻咽喉头颈外科,上海200233

出　　处：《中华耳科学杂志》2021年第4期683-687,共5页Chinese Journal of Otology

基　　金：国家自然科学基金(81770998)。

摘　　要：在内毛细胞(inner hair cell,IHCs)中,突触对声音的启动做出反应,驱动受神经支配的螺旋神经节神经元(spiral ganglion neurons,SGN)以kHz为单位的频率产生动作电位,并支持以几百赫兹的频率对持续的声音进行反应。我们认为突触前带状结构和其他特殊的分子组成是获得这些功能特征的基础。然而,确切的潜在机制并不完全清楚,但一定与带状突触的特殊分子和结构特征有关。本文主要针对最近内毛细胞带状突触的钙离子通道相关的研究进行总结。在Ca^(2+)通道-胞吐作用偶联方面,内毛细胞中巴松管或带状结构以及RIM2α和β的位置决定了钙通道的正确分布,且在面向蜗轴一侧的钙通道密度高并连接低具有高阈值的自发放电率纤维;而远离蜗轴侧的钙通道密度小并连接具有低阈值的高自发放电纤维。除此之外,多种蛋白同样参与到这个过程中,如Piccolino及harmonin等。去极化过程中,钙主要通过CaV1.3 L型Ca^(2+)通道内流,其耦合方式分为:单纯Ca^(2+)纳米域控制或单纯Ca^(2+)微米域控制。根据成熟以及非成熟激活域(active zone,AZ)胞吐的生物物理模型,在发育过程中,偶联方式由Ca^(2+)的微米域控制向Ca^(2+)的纳米域控制转变。内源性Ca^(2+)缓冲是突触信号传导的关键一环,对于频率调谐及传入突触传递和传出调制至关重要。EF-hand Ca^(2+)结合蛋白作为钙缓冲成分可以调节突触前内毛细胞功能以实现代谢上有效的声音编码。In inner hair cells(IHCs),the synapse responds to sound onset driving the innervated SGN to produce action potentials at kHz rate and supports firing at a rate of hundreds of hertz in response to ongoing sound.It is believed that the presynaptic ribbon and other special molecular composition are the base for achieving such functional features.However,exact underlying mechanisms are not entirely clear and remain enigmatic but must be related to the special molecular and structural features in ribbon synapses.This review summarizes recent studies on ribbon synapses related Ca^(2+)channels in inner hair cells.In terms of Ca^(2+)channel-exocytosis coupling,the clustering of Ca^(2+)channel depends on multiple molecular scaffolds,including Bassoon,or ribbon as well as RIM2αandβin the inner hair cells.The modiolar side is thought to have more Ca^(2+)channels driving low-spontaneous-rate,high-threshold SGNs,while the pillar side has less Ca^(2+)channels,which drive high-spontaneous-rate,low-threshold SGNs.In addition,a variety of proteins are also involved in Ca^(2+)channel-exocytosis coupling,such as Piccolino and harmonin.During the depolarization process,calcium mainly flows in through the CaV1.3 L-type Ca^(2+)channel,and the coupling mode can be distinguished as two limiting cases:“pure”Ca^(2+)nanodomain control or“pure”Ca^(2+)microdomain control.Based upon biophysical modeling of exocytosis at mature and immature active zones,during the development process,the coupling mode changes from the Ca^(2+)nanodomain control to the Ca^(2+)microdomain control.Endogenous Ca^(2+)buffering is a key part of synaptic signal transmission,which is essential for frequency tuning and afferent synaptic transmission and efferent modulation.As a Ca^(2+)buffer,EF-hand Ca^(2+)-binding proteins can regulate presynaptic IHC function for metabolically efficient sound coding.

关 键 词：内毛细胞 带状突触 钙离子通道 突触囊泡 内耳 

分 类 号：R764[医药卫生—耳鼻咽喉科]