Overexpression of SK2 channels enhances efferent suppression of cochlear responses without enhancing noise resistance
Overexpression of SK2 channels enhances efferent suppression of cochlear responses without enhancing noise resistance
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DOI：
10.1152/jn.01183.2006
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发表时间：
2007-04-01
影响因子：
2.5
通讯作者：
Liberman, M. Charles
中科院分区：
文献类型：
--
作者：
Maison, Stephane F.;Parker, Lisan L.;Liberman, M. Charles
耳蜗毛细胞表达SK 2，这是一种小电导钙激活的K+通道，被认为与钙渗透性烟碱乙酰胆碱受体（nAChRs）α 9和α 10协同作用，介导橄榄耳蜗传出神经支配的抑制作用。为了探索SK2通道在听觉中的体内作用，我们研究了过表达SK2通道的小鼠的基因表达、耳蜗功能、传出抑制和噪声脆弱性。通过听觉脑干反应和耳声发射测量的耳蜗阈值在过表达者中是正常的，因为整体耳蜗形态和外毛细胞传出末梢的大小、数量和分布也是正常的。SK2通道的相关蛋白表达水平升高了8倍，而其他SK通道或α 9/α 10 nAChR没有显著变化。如先前在α 9过表达小鼠中所见，过表达小鼠中耳蜗反应的休克诱发的传出抑制显著增强;然而，与α 9过表达者相反，SK 2过表达者不受声损伤的保护。结果表明，传出介导的耳蜗保护介导的其他下游影响乙酰胆碱介导的Ca 2+进入不同的SK 2介导的超极化和相关的减少外毛细胞电活动。
Cochlear hair cells express SK2, a small-conductance Ca2+-activated K+ channel thought to act in concert with Ca2+-permeable nicotinic acetylcholine receptors (nAChRs) alpha 9 and alpha 10 in mediating suppressive effects of the olivocochlear efferent innervation. To probe the in vivo role of SK2 channels in hearing, we examined gene expression, cochlear function, efferent suppression, and noise vulnerability in mice overexpressing SK2 channels. Cochlear thresholds, as measured by auditory brain stem responses and otoacoustic emissions, were normal in overexpressers as was overall cochlear morphology and the size, number, and distribution of efferent terminals on outer hair cells. Cochlear expression levels of SK2 channels were elevated eightfold without striking changes in other SK channels or in the alpha 9/alpha 10 nAChRs. Shock-evoked efferent suppression of cochlear responses was significantly enhanced in overexpresser mice as seen previously in alpha 9 overexpresser mice; however, in contrast to alpha 9 overexpressers, SK2 overexpressers were not protected from acoustic injury. Results suggest that efferent-mediated cochlear protection is mediated by other downstream effects of ACh-mediated Ca2+ entry different from those involving SK2-mediated hyperpolarization and the associated reduction in outer hair cell electromotility.