Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea
Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea
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DOI：
10.1523/jneurosci.0123-05.2005
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发表时间：
2005-07-20
影响因子：
5.3
通讯作者：
Morest, DK
中科院分区：
文献类型：
--
作者：
Hossain, WA;Antic, SD;Morest, DK
耳蜗肌动作电位的起源一直是个谜。由于电压依赖性钠离子(NAV)通道是动作电位产生所必需的，我们研究了NA1.6和NA1.2在耳蜗神经节、耳蜗神经和Corti器中的详细分布，包括I型和II型神经节细胞。在大多数I型神经节细胞中，Nav1.6存在于有髓双极细胞体两侧的第一个结节和Ranvier的后续结节。在其他神经节细胞中，包括II型，Nav1.6聚集在无髓双极神经节细胞体两侧的两个轴突的起始段。在Corti器中，Nav1.6定位于各内毛细胞下方的传入轴突及其感觉末梢的短段。令人惊讶的是，外螺旋纤维及其感觉末梢在整个轨迹上都被标记在外毛细胞的下方。相反，在Corti器官中的Nav1.2定位于内、外毛细胞上的无髓传出轴突及其终末。我们提出了一个计算模型，说明了这里描述的NAV通道分布的潜在作用。在颤抖失聪突变小鼠中，Nav1.6在感觉上皮和神经节中的定位被破坏。综上所述，这些结果表明，不同的NAV通道在耳蜗神经节细胞和神经纤维的多个部位产生和再生动作电位，包括传入终末、神经节起始段和Ranvier结节。
The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.