Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells
Developmental changes in the expression of potassium currents of embryonic, neonatal and mature mouse inner hair cells
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DOI：
10.1113/jphysiol.2002.034801
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发表时间：
2003-04-15
影响因子：
5.5
通讯作者：
Kros, CJ
中科院分区：
文献类型：
--
作者：
Marcotti, W;Johnson, SL;Kros, CJ
研究了小鼠耳蜗内毛细胞（IHC）从终末分化到功能成熟的电生理特性的发育变化。早在胚胎第14.5天（E14.5），新分化的IHC表达一个非常小的外向K+电流，这在很大程度上是不敏感的4-氨基吡啶（4-AP）。一天后，首次观察到内向整流器I-K1。这些未成熟的细胞在电流钳下最初仅表现出缓慢的分级电压响应。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K+电流的大小稳步增加，电流的一个渐进的更大的部分是敏感的4-AP。在出生后第二周，激活的4-AP敏感电流，现在贡献了约一半的外向K+电流，超极化方向的转变。与I-K1大小的增加一起，这使细胞超极化，从而抑制自发峰电位活动，尽管在去极化电流注入时仍然可以诱发峰电位。从听力开始（出生后第12天，P12）开始，不成熟的IHC向具有快速分级电压响应的完全功能的感觉受体迈出了最后的一步。这主要是通过表达大电导Ca 2+激活的K+电流I-K，I-f来实现的，但也可以表达与先前在成熟外毛细胞（OHC）中描述的负激活I-K，I-n不可区分的电流。4-AP敏感电流在听觉开始后继续增加，形成成熟的延迟整流器I-K、I-s的主要部分。到P20，IHC在K+电导的补充方面似乎成熟。
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, I-Kl, 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 I-Kl, 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 I-K,I-f, but also of a current indistinguishable from the negatively activating I-K,I-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, I-K,I-s. By P20 IHCs appear mature in terms of their complement of K+ conductances.