生物谷報(bào)道：美國西北大學(xué)科研人員近日研究發(fā)現(xiàn)遺傳變異和過量使用藥物引起聽力受損的原因,。耳蝸中的一個(gè)電放大機(jī)制是人類和其他動(dòng)物有敏銳聽力的關(guān)鍵。這一研究結(jié)果使我們清楚地了解了遺傳變異和過量使用藥物,，如阿司匹林是如何損害這一放大機(jī)制引起聽力喪失的,。
聲音進(jìn)入耳朵被耳蝸中毛細(xì)胞伸展出來的纖毛通過振動(dòng)而感知。耳蝸的內(nèi)毛細(xì)胞只是一個(gè)被動(dòng)感受器,，而外毛細(xì)胞在將震動(dòng)轉(zhuǎn)變成電信號(hào)傳到大腦聽覺中樞時(shí)把聲音進(jìn)行了放大,。沒有外毛細(xì)胞的放大作用，聽覺就不會(huì)靈敏,，因?yàn)槁暡ㄟM(jìn)入耳蝸后,，內(nèi)耳的液體會(huì)將能量嚴(yán)重削弱。
這次研究的目的就是探尋外毛細(xì)胞的放大機(jī)制,，特別是想?yún)^(qū)分過去聽覺機(jī)制研究中的兩個(gè)放大理論,，“靜纖毛運(yùn)動(dòng)”和“體細(xì)胞運(yùn)動(dòng)”。
靜纖毛理論認(rèn)為,，聲波的放大是通過復(fù)雜的外毛細(xì)胞上的纖毛束波動(dòng)實(shí)現(xiàn)的,。體細(xì)胞運(yùn)動(dòng)理論則認(rèn)為，聲音信號(hào)是通過鑲嵌在毛細(xì)胞膜中的叫做壓力素（Prestin）的放大器蛋白進(jìn)行放大的,。壓力素是通過細(xì)胞膜中因聲波機(jī)械振動(dòng)所產(chǎn)生的電壓提供動(dòng)力的,。
壓力素蛋白是體細(xì)胞運(yùn)動(dòng)的關(guān)鍵因素，研究人員在過去的實(shí)驗(yàn)中將小鼠的壓力素蛋白敲除掉,，以觀察對(duì)聽覺的影響,。結(jié)果發(fā)現(xiàn)，這些小鼠聽力出現(xiàn)了問題,，說明細(xì)胞體運(yùn)動(dòng)失去了作用,。盡管試驗(yàn)有力證明了細(xì)胞體運(yùn)動(dòng)的作用，但這些小鼠的外毛細(xì)胞也出現(xiàn)了結(jié)構(gòu)異常,，這更使問題復(fù)雜化了,。在對(duì)細(xì)胞體運(yùn)動(dòng)的進(jìn)一步研究中，研究人員對(duì)壓力蛋白做了細(xì)微的改變,。他們只去掉了它的放大作用,，而不影響外毛細(xì)胞的結(jié)構(gòu)或功能。結(jié)果顯示,，與敲除壓力素蛋白結(jié)果一樣,，這些小鼠出現(xiàn)同樣的聽力損失,。這就消除了對(duì)以前試驗(yàn)的疑問，確信了外毛細(xì)胞的細(xì)胞體運(yùn)動(dòng)在耳蝸的放大機(jī)制中起了重要作用,。
但是這些研究結(jié)果仍不能排除靜纖毛運(yùn)動(dòng)對(duì)耳蝸放大作用所起的影響,，因?yàn)橄?xì)胞體運(yùn)動(dòng)的同時(shí)也削弱了纖毛的運(yùn)動(dòng)。因此,，這兩種 運(yùn)動(dòng)形式不能孤立開來,。研究人員推測(cè)，這兩種機(jī)制從不同的方面發(fā)揮了放大作用,。
壓力素對(duì)聽覺所起的作用有助于幫助科學(xué)家更好了解聽覺損失的機(jī)制,。例如，過量的阿司匹林通過抑制壓力素引起高頻聽力損失,。許多高頻聽力喪失的病例也是由于與壓力素有關(guān)的細(xì)胞分子機(jī)制缺陷造成的,。兩種壓力素基因變異也與耳聾有關(guān)。生物谷(www.bioon.com)
生物谷推薦原始出處：
Neuron. 2008 May 8; 58(3):333-9.
Prestin-based outer hair cell motility is necessary for Mammalian cochlear amplification
Dallos P, Wu X, Cheatham MA, Gao J, Zheng J, Anderson CT, Jia S, Wang X, Cheng WH, Sengupta S, He DZ, Zuo J
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA; Department of Communication Sciences and Disorders, The Hugh Knowles Center, Northwestern University, Evanston, IL 60208, USA.
It is a central tenet of cochlear neurobiology that mammalian ears rely on a local, mechanical amplification process for their high sensitivity and sharp frequency selectivity. While it is generally agreed that outer hair cells provide the amplification, two mechanisms have been proposed: stereociliary motility and somatic motility. The latter is driven by the motor protein prestin. Electrophysiological phenotyping of a prestin knockout mouse intimated that somatic motility is the amplifier. However, outer hair cells of knockout mice have significantly altered mechanical properties, making this mouse model unsatisfactory. Here, we study a mouse model without alteration to outer hair cell and organ of Corti mechanics or to mechanoelectric transduction, but with diminished prestin function. These animals have knockout-like behavior, demonstrating that prestin-based electromotility is required for cochlear amplification.
