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胚胎、新生和成熟小鼠内毛细胞钾电流表达的发育变化。

Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells.

作者信息

Marcotti Walter, Johnson Stuart L, Holley Matthew C, Kros Corné J

机构信息

School of Biological Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK.

出版信息

J Physiol. 2003 Apr 15;548(Pt 2):383-400. doi: 10.1113/jphysiol.2002.034801. Epub 2003 Feb 14.

Abstract

Developmental changes in electrophysiological membrane properties of mouse cochlear inner hair cells (IHCs) were studied from just after terminal differentiation up to functional maturity. As early as embryonic day 14.5 (E14.5) newly differentiated IHCs express a very small outward K+ current that is largely insensitive to 4-aminopyridine (4-AP). One day later the inward rectifier, IK1, is first observed. These immature cells initially exhibit only slow graded voltage responses under current clamp. From E17.5 spontaneous action potentials occur. During the first week of postnatal development, the outward K+ current steadily increases in size and a progressively larger fraction of the current is sensitive to 4-AP. During the second postnatal week, the activation of the 4-AP-sensitive current, by now contributing about half of the outward K+ current, shifts in the hyperpolarizing direction. Together with an increase in size of IK1, this hyperpolarizes the cell, thus inhibiting the spontaneous spike activity, although spikes could still be evoked upon depolarizing current injection. Starting at about the onset of hearing (postnatal day 12, P12) immature IHCs make the final steps towards fully functional sensory receptors with fast graded voltage responses. This is achieved mainly by the expression of the large-conductance Ca2+-activated K+ current IK,f, but also of a current indistinguishable from the negatively activating IK,n previously described in mature outer hair cells (OHCs). The 4-AP-sensitive current continues to increase after the onset of hearing to form the major part of the mature delayed rectifier, IK,s. By P20 IHCs appear mature in terms of their complement of K+ conductances.

摘要

从小鼠耳蜗内毛细胞(IHC)终末分化后直至功能成熟,对其电生理膜特性的发育变化进行了研究。早在胚胎第14.5天(E14.5),新分化的内毛细胞就表达一种非常小的外向钾离子电流,该电流对4-氨基吡啶(4-AP)基本不敏感。一天后首次观察到内向整流钾电流IK1。这些未成熟细胞在电流钳制下最初仅表现出缓慢的分级电压反应。从E17.5开始出现自发动作电位。在出生后发育的第一周,外向钾离子电流的大小稳步增加,且电流中对4-AP敏感的部分逐渐增多。在出生后的第二周,此时对4-AP敏感的电流已占外向钾离子电流的约一半,其激活向超极化方向移动。随着IK1大小的增加,这使细胞超极化,从而抑制自发的尖峰活动,尽管在注入去极化电流时仍可诱发尖峰。大约从听力开始(出生后第12天,P12)起,未成熟的内毛细胞向具有快速分级电压反应的完全功能性感觉受体迈出最后几步。这主要通过大电导钙激活钾电流IK,f的表达实现,但也通过一种与之前在成熟外毛细胞(OHC)中描述的负激活IK,n无法区分的电流实现。听力开始后,对4-AP敏感的电流继续增加,形成成熟延迟整流钾电流IK,s的主要部分。到P20时,内毛细胞在钾离子电导方面看起来已成熟。

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