Hossain Waheeda A, Antic Srdjan D, Yang Yang, Rasband Matthew N, Morest D Kent
Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
J Neurosci. 2005 Jul 20;25(29):6857-68. doi: 10.1523/JNEUROSCI.0123-05.2005.
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.
耳蜗动作电位的起源一直是个长期存在的谜题。由于电压依赖性钠离子（Nav）通道对于动作电位的产生至关重要，我们研究了Nav1.6和Nav1.2在耳蜗神经节、耳蜗神经以及柯蒂氏器中的详细分布情况，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存在于有髓鞘双极细胞体两侧的第一个结以及随后的郎飞结处。在其他神经节细胞中，包括II型细胞，Nav1.6聚集在无髓鞘双极神经节细胞体两侧轴突的起始段。在柯蒂氏器中，Nav1.6定位于每个内毛细胞下方传入轴突的短段及其感觉末梢。令人惊讶的是，外螺旋纤维及其感觉末梢在其整个轨迹上的外毛细胞下方都有良好的标记。相比之下，柯蒂氏器中的Nav1.2定位于无髓鞘传出轴突及其在内毛细胞和外毛细胞上的末梢。我们提出了一个计算模型来说明此处描述的Nav通道分布的潜在作用。在耳聋突变颤抖小鼠中，Nav1.6在感觉上皮和神经节中的定位被破坏。总之，这些结果表明，不同的Nav通道在沿耳蜗神经节细胞和神经纤维的多个部位产生并再生动作电位，包括传入末梢、神经节起始段和郎飞结。
