耳蜗毛细胞机械传感器通道的发育变化及其跨膜通道样蛋白的调控。

Kyunghee X Kim, Robert Fettiplace
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引用次数: 91

摘要

立体纤毛束的振动激活钙渗透性机械换能器(MT)通道,启动耳蜗毛细胞的声音检测。耳蜗的不同区域对不同的声波频率有优先反应,耳蜗通道的单一电导的变化有助于这种异位组织。尽管MT通道的分子身份仍不确定,但跨膜通道家族的两个成员,Tmc1和Tmc2,对毛细胞的机械转导至关重要。我们测量了野生型小鼠和缺乏Tmc1 (Tmc1-/-)或Tmc2 (Tmc2-/-)小鼠在出生后发育期间沿耳蜗纵轴(张力异位)轴的MT通道电流振幅和Ca(2+)通透性。在出生后4天(P)以上的野生型小鼠中,外耳毛细胞(OHCs)从耳蜗尖端到耳蜗基部的MT电流振幅增加了约1.5倍,而内耳毛细胞(IHCs)的MT电流振幅变化不大,这一模式在突变小鼠出生后第一周内明显存在。P7后,Tmc1-/- (dn)小鼠的OHC MT电流降至零,与耳聋表型一致。P6前野生型小鼠,OHC - MT通道的相对Ca(2+)通透性P(Ca)由耳蜗尖向耳蜗底递减。这种P(Ca)梯度在ihc中不明显,在OHCs中P7后消失。Tmc1-/-小鼠基底OHCs的P(Ca)值高于野生型小鼠(与根尖OHCs相等),而Tmc2-/-小鼠的基底OHCs和ihc的P(Ca)值低于野生型小鼠。我们假设Ca(2+)渗透性的差异反映了由Tmc1和Tmc2表达决定的MT通道的不同亚基组成,后者在ihc和未成熟的顶端OHCs中赋予更高的P(Ca)。随着成熟P(Ca)的变化与OHCs中而ihc中Tmc2丰度的发育减少一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel-like proteins.

Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel-like proteins.

Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel-like proteins.

Developmental changes in the cochlear hair cell mechanotransducer channel and their regulation by transmembrane channel-like proteins.

Vibration of the stereociliary bundles activates calcium-permeable mechanotransducer (MT) channels to initiate sound detection in cochlear hair cells. Different regions of the cochlea respond preferentially to different acoustic frequencies, with variation in the unitary conductance of the MT channels contributing to this tonotopic organization. Although the molecular identity of the MT channel remains uncertain, two members of the transmembrane channel-like family, Tmc1 and Tmc2, are crucial to hair cell mechanotransduction. We measured MT channel current amplitude and Ca(2+) permeability along the cochlea's longitudinal (tonotopic) axis during postnatal development of wild-type mice and mice lacking Tmc1 (Tmc1-/-) or Tmc2 (Tmc2-/-). In wild-type mice older than postnatal day (P) 4, MT current amplitude increased ~1.5-fold from cochlear apex to base in outer hair cells (OHCs) but showed little change in inner hair cells (IHCs), a pattern apparent in mutant mice during the first postnatal week. After P7, the OHC MT current in Tmc1-/- (dn) mice declined to zero, consistent with their deafness phenotype. In wild-type mice before P6, the relative Ca(2+) permeability, P(Ca), of the OHC MT channel decreased from cochlear apex to base. This gradient in P(Ca) was not apparent in IHCs and disappeared after P7 in OHCs. In Tmc1-/- mice, P(Ca) in basal OHCs was larger than that in wild-type mice (to equal that of apical OHCs), whereas in Tmc2-/-, P(Ca) in apical and basal OHCs and IHCs was decreased compared with that in wild-type mice. We postulate that differences in Ca(2+) permeability reflect different subunit compositions of the MT channel determined by expression of Tmc1 and Tmc2, with the latter conferring higher P(Ca) in IHCs and immature apical OHCs. Changes in P(Ca) with maturation are consistent with a developmental decrease in abundance of Tmc2 in OHCs but not in IHCs.

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