Tonotopic Gradient in the Developmental Acquisition of Sensory Transduction in Outer Hair Cells of the Mouse Cochlea

Tonotopic Gradient in the Developmental Acquisition of Sensory Transduction in Outer Hair Cells of the Mouse Cochlea
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DOI:
10.1152/jn.00136.2009
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发表时间:
2009-06-01
影响因子:
2.5
通讯作者:
Geleoc, Gwenaeelle S. G.
Geleoc, Gwenaeelle S. G.
中科院分区:
医学3区
文献类型:
--
作者:
Lelli, Andrea;Asai, Yukako;Geleoc, Gwenaeelle S. G.

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Lelli A,Asai Y,Forge A,Holt JR,Geleoc GS.小鼠耳蜗外毛细胞感觉传导发育获得中的音调梯度。神经生理学杂志101:2961-2973,2009年。首次发表于2009年4月1日; doi:10.1152/jn.00136.2009。内耳毛细胞是一种精密的机械传感器,可以将其感觉毛束的纳米级偏转转化为电信号。在发育过程中必须精确地组装几个基本元件,以赋予机械转导装置的独特结构和功能。在这里,我们调查的功能发展的外毛细胞的转导复合物沿着小鼠耳蜗急性切除胚胎第17天(E17)和出生后第8天(P8)之间的长度。我们用扫描电子显微镜绘制了静纤毛束的发展; FM 1 -43摄取,其渗透毛细胞转导通道,由快速毛束偏转引起的机械转导电流,以及转导复合物的可能组分的mRNA表达。我们证明,FM 1 -43的摄取首先发生在耳蜗的基底部分在P0和进展向顶点在随后的一周。从234个外毛细胞E17和P8从四个耳蜗区域之间获得的电生理记录显示FM 1 -43摄取模式和机械转导的收购之间的相关性。我们发现了一个时空梯度的属性转导,包括发病,幅度,操作范围,时间过程中,适应的程度。我们使用定量RT-PCR检测几种毛细胞肌球蛋白和候选tip-link分子的相对mRNA表达。我们发现了编码钙粘蛋白23,原钙粘蛋白15,肌球蛋白3a,7a,15 a和PMCA 2的mRNA的时空表达模式,之前收购的转导。肌球蛋白1c和PMCA 2 mRNA的时空表达模式与力学转导的几个属性的发育变化相关。
Lelli A, Asai Y, Forge A, Holt JR, Geleoc GS. Tonotopic gradient in the developmental acquisition of sensory transduction in outer hair cells of the mouse cochlea. J Neurophysiol 101: 2961-2973, 2009. First published April 1, 2009; doi: 10.1152/jn.00136.2009. Inner ear hair cells are exquisite mechanosensors that transduce nanometer scale deflections of their sensory hair bundles into electrical signals. Several essential elements must be precisely assembled during development to confer the unique structure and function of the mechanotransduction apparatus. Here we investigated the functional development of the transduction complex in outer hair cells along the length of mouse cochlea acutely excised between embryonic day 17 (E17) and postnatal day 8 (P8). We charted development of the stereociliary bundle using scanning electron microscopy; FM1-43 uptake, which permeates hair cell transduction channels, mechanotransduction currents evoked by rapid hair bundle deflections, and mRNA expression of possible components of the transduction complex. We demonstrated that uptake of FM1-43 first occurred in the basal portion of the cochlea at P0 and progressed toward the apex over the subsequent week. Electrophysiological recordings obtained from 234 outer hair cells between E17 and P8 from four cochlear regions revealed a correlation between the pattern of FM1-43 uptake and the acquisition of mechanotransduction. We found a spatiotemporal gradient in the properties of transduction including onset, amplitude, operating range, time course, and extent of adaptation. We used quantitative RT-PCR to examine relative mRNA expression of several hair cell myosins and candidate tip-link molecules. We found spatiotemporal expression patterns for mRNA that encodes cadherin 23, protocadherin 15, myosins 3a, 7a, 15a, and PMCA2 that preceded the acquisition of transduction. The spatiotemporal expression patterns of myosin 1c and PMCA2 mRNA were correlated with developmental changes in several properties of mechanotransduction.