生物谷綜合：過去30年間,，科學(xué)家們一直都在爭論哺乳動物耳蝸外毛細(xì)胞（outerhaircells）如何擴增聽力的，來自美國圣猶大兒童研究醫(yī)院（St.JudeChildren’sResearchHospital）,，美國克瑞屯大學(xué)（CreightonUniversity）,，西北大學(xué)神經(jīng)生物學(xué)與生理學(xué)系的研究人員將突變引入到了胚胎干細(xì)胞，獲得了一種只包含prestin突變的遺傳工程小鼠,，從而認(rèn)為體細(xì)胞運動也許是哺乳動物耳蝸聲音擴增過程中的關(guān)鍵因子,。
文章的通訊作者是來自美國圣猶大兒童研究醫(yī)院的左鍵博士,，其早年畢業(yè)于華中科技大學(xué)，于加州大學(xué)舊金山分校獲得了博士學(xué)位,。
耳蝸（Cochlea）是內(nèi)耳的一個解剖結(jié)構(gòu),，它和前庭迷路一起組成內(nèi)耳骨迷路。耳蝸的名稱來源于其形狀與蝸牛殼的相似性,，耳蝸的英文名Cochlea,，即是拉丁語中“蝸牛殼”的意思。耳蝸是外周聽覺系統(tǒng)的組成部分,。其核心部分為柯蒂氏器（OrganofCorti）,，是聽覺轉(zhuǎn)導(dǎo)器官，負(fù)責(zé)將來自中耳的聲音信號轉(zhuǎn)換為相應(yīng)的神經(jīng)電信號,，交送腦的中樞聽覺系統(tǒng)接受進一步處理,，最終實現(xiàn)聽覺知覺。耳蝸的病變和多種聽覺障礙密切相關(guān),。
耳蝸位于顳骨（Temporalbone）深處,，毗鄰中耳聽骨鏈和腦干，和是內(nèi)耳骨迷路的組成部分,。耳蝸的幾何對稱軸,，稱為耳蝸軸（Modiolus）大致處在水平面內(nèi)，與顳骨表面垂直,。前庭耳蝸神經(jīng)與聽覺相關(guān)的一部分：耳蝸神經(jīng),，起源自耳蝸。
耳蝸的蝸牛形狀只在哺乳類動物存在,，一些其他動物的耳蝸雖然不具有螺旋形狀（例如鳥類的線形耳蝸）,，但是仍然稱為“耳蝸”。
毛細(xì)胞（Haircells）規(guī)則地分布于基底膜之上,，自耳蝸底端至頂端的全長范圍內(nèi)形成平行的四列,。其中靠近耳蝸中心的一列稱為內(nèi)毛細(xì)胞（Innerhaircells）；遠(yuǎn)離中心的三列稱為外毛細(xì)胞（Outerhaircells）,。
兩類毛細(xì)胞的頂部都有若干列靜纖毛（Stereocilia）,，同時有少量動纖毛（Kinocilia）（只在發(fā)育中的毛細(xì)胞存在）。當(dāng)外淋巴在機械震動下帶動蓋膜和基底膜形成相對剪切運動時,，纖毛發(fā)生搖擺,。纖毛的搖擺通過一些尚未研究透徹的機制，導(dǎo)致纖毛頂部附近的離子通道的開閉,，形成跨膜電流和感受器電位,。
內(nèi)毛細(xì)胞是感受器細(xì)胞，與若干個聽神經(jīng)纖維形成突觸連接,。負(fù)責(zé)將機械振動轉(zhuǎn)化為與之相連的聽神經(jīng)纖維的動作電位,。外毛細(xì)胞與來自
上橄欖核的傳出神經(jīng)以及另一類型的傳入神經(jīng)（稱為II型傳入纖維）形成突觸,，其生理功能尚不完全清楚，一般認(rèn)為與增強聽神經(jīng)的高度頻率選擇性,、耳蝸的調(diào)節(jié)和自我保護機制有關(guān),。
過去30年間，科學(xué)家們一直都在爭論哺乳動物耳蝸外毛細(xì)胞（outerhaircells）如何擴增聽力的,，目前有兩種流行的機制,。當(dāng)聲音到達(dá)耳蝸的時候，毛細(xì)胞以刺激頻率隨著聲音長度震蕩,，這種“體細(xì)胞運動”（somaticmotility）只在哺乳動物中發(fā)現(xiàn)過,，被認(rèn)為是由動力蛋白prestin驅(qū)動的，位于毛細(xì)胞基層的纖毛也隨之振動,。
雖然是否體細(xì)胞運動只存在于纖毛驅(qū)動的擴增器中是一個懸而未決的問題,，但是高建鋼（JiangangGao，音譯）等人在實驗中發(fā)現(xiàn)事實并不是如此,。野生型毛細(xì)胞在得到聲音信號后會縮短,，并且在這種減少了長度周圍震蕩。相反表達(dá)之前發(fā)現(xiàn)的prestin突變的毛細(xì)胞則在增加長度周圍震蕩,，因此突變細(xì)胞中纖毛的位置是有偏向性的,，如果這種偏向改變了纖毛的擴增，那么突變動物中的聽力就會受到影響,。
所以,，在這篇文章中，研究人員將突變引入到了胚胎干細(xì)胞,，獲得了一種只包含prestin突變的遺傳工程小鼠,，這些小鼠中毛細(xì)胞的有關(guān)實驗則表明反應(yīng)頻率是正常的，聽力也沒發(fā)現(xiàn)改變,。因此研究人員認(rèn)為體細(xì)胞運動也許在哺乳動物耳蝸聲音擴增過程中占主導(dǎo)調(diào)控地位,。
原始出處:
Published online before print July 18, 2007, 10.1073/pnas.0700356104
PNAS | July 24, 2007 | vol. 104 | no. 30 | 12542-12547
BIOLOGICAL SCIENCES / NEUROSCIENCE
Prestin-based outer hair cell electromotility in knockin mice does not appear to adjust the operating point of a cilia-based amplifier
Jiangang Gao*, Xiang Wang, Xudong Wu*, Sal Aguinaga, Kristin Huynh, Shuping Jia, Keiji Matsuda, Manish Patel*, Jing Zheng, MaryAnn Cheatham, David Z. He, Peter Dallos,, and Jian Zuo*,*,¶
*Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105; Department of Biomedical Sciences, Creighton University, Omaha, NE 68178; and Departments of Communication Sciences and Disorders and Neurobiology and Physiology, Northwestern University, Evanston, IL 60208
Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved May 18, 2007 (received for review January 15, 2007)
The remarkable sensitivity and frequency selectivity of the mammalian cochlea is attributed to a unique amplification process that resides in outer hair cells (OHCs). Although the mammalian-specific somatic motility is considered a substrate of cochlear amplification, it has also been proposed that somatic motility in mammals simply acts as an operating-point adjustment for the ubiquitous stereocilia-based amplifier. To address this issue, we created a mouse model in which a mutation (C1) was introduced into the OHC motor protein prestin, based on previous results in transfected cells. In C1/C1 knockin mice, localization of C1-prestin, as well as the length and number of OHCs, were all normal. In OHCs isolated from C1/C1 mice, nonlinear capacitance and somatic motility were both shifted toward hyperpolarization, so that, compared with WT controls, the amplitude of cycle-by-cycle (alternating, or AC) somatic motility remained the same, but the unidirectional (DC) component reversed polarity near the OHC's presumed in vivo resting membrane potential. No physiological defects in cochlear sensitivity or frequency selectivity were detected in C1/C1 or C1/+ mice. Hence, our results do not support the idea that OHC somatic motility adjusts the operating point of a stereocilia-based amplifier. However, they are consistent with the notion that the AC component of OHC somatic motility plays a dominant role in mammalian cochlear amplification.
cochlear amplification | mechanosensory | prestin
