Developmental alterations in the biophysical properties of Ca(v) 1.3 Ca(2+) channels in mouse inner hair cells.
Developmental alterations in the biophysical properties of Ca(v) 1.3 Ca(2+) channels in mouse inner hair cells.
复制标题
DOI：
10.4161/chan.24104
复制
发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Lee A
中科院分区：
文献类型：
--
作者：
Inagaki A;Lee A
在听力发作之前，自发动作电位激活小鼠内毛细胞（IHCs）中的电压门控Cav1.3 Ca2+通道，从而触发谷氨酸的胞分泌和传入神经元的兴奋。在成熟的ihc中，Cav1.3通道响应诱发受体电位打开，导致准确声音传输所需的胞吐梯度变化。Cav1.3特性的发育改变可能支持Cav1.3在未成熟和成熟IHCs中的不同作用，并且在各种物种中都有报道。目前尚不清楚小鼠ihc中是否会发生Cav1.3性质的变化，但这对于理解Cav1.3在ihc发育和成熟中的作用是必要的。在这里，我们描述了小鼠ihc中Cav1.3通道生物物理特性的年龄依赖性差异。在成熟的IHCs中，Cav1.3通道比未成熟的IHCs激活更快，并且表现出更大的Ca2+依赖性失活（CDI）。与异种表达系统中Cav1.3通道的特性一致，成熟ihc中的CDI不受细胞内Ca2+缓冲强度增加的影响。然而，未成熟ihc中的CDI通过细胞内强Ca2+缓冲显著降低，这既减缓了失活的发生，又加速了失活的恢复。这些结果表明CDI对Ca2+整体升高的敏感性在发育过程中下降，这限制了成熟ihc中Cav1.3通道对传入Ca2+离子的负反馈调节。与更快的Cav1.3激活动力学一起，Cav1.3 CDI对局部Ca2+的依赖性增加可能会增强突触前Ca2+信号，并改善成熟ihc中声音编码的时间方面。
Prior to hearing onset, spontaneous action potentials activate voltage-gated Cav1.3 Ca2+ channels in mouse inner hair cells (IHCs), which triggers exocytosis of glutamate and excitation of afferent neurons. In mature IHCs, Cav1.3 channels open in response to evoked receptor potentials, causing graded changes in exocytosis required for accurate sound transmission. Developmental alterations in Cav1.3 properties may support distinct roles of Cav1.3 in IHCs in immature and mature IHCs, and have been reported in various species. It is not known whether such changes in Cav1.3 properties occur in mouse IHCs, but this knowledge is necessary for understanding the roles of Cav1.3 in developing and mature IHCs. Here, we describe age-dependent differences in the biophysical properties of Cav1.3 channels in mouse IHCs. In mature IHCs, Cav1.3 channels activate more rapidly and exhibit greater Ca2+-dependent inactivation (CDI) than in immature IHCs. Consistent with the properties of Cav1.3 channels in heterologous expression systems, CDI in mature IHCs is not affected by increasing intracellular Ca2+ buffering strength. However, CDI in immature IHCs is significantly reduced by strong intracellular Ca2+ buffering, which both slows the onset of, and accelerates recovery from, inactivation. These results signify a developmental decline in the sensitivity of CDI to global elevations in Ca2+, which restricts negative feedback regulation of Cav1.3 channels to incoming Ca2+ ions in mature IHCs. Together with faster Cav1.3 activation kinetics, increased reliance of Cav1.3 CDI on local Ca2+ may sharpen presynaptic Ca2+ signals and improve temporal aspects of sound coding in mature IHCs.
登录
查看更多内容
影响因子：
2.5
作者：
Grant, Lisa;Fuchs, Paul
通讯作者：
Fuchs, Paul
影响因子：
25
作者：
Gregory FD;Bryan KE;Pangršič T;Calin-Jageman IE;Moser T;Lee A
通讯作者：
Lee A
DOI：
10.1523/jneurosci.1866-11.2011
发表时间：
2011-11-16
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Graydon CW;Cho S;Li GL;Kachar B;von Gersdorff H
通讯作者：
von Gersdorff H
影响因子：
3
作者：
Christel, Carl;Lee, Amy
通讯作者：
Lee, Amy
影响因子：
5.3
作者：
Goutman, Juan D.
通讯作者：
Goutman, Juan D.