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Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

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.

Pubmed ID: 16033895 RIS Download

Mesh terms: Action Potentials | Animals | Axons | Cochlear Nerve | Deafness | Female | Hair Cells, Auditory | Male | Mice | Mice, Inbred C57BL | Mice, Inbred CBA | Mice, Neurologic Mutants | NAV1.2 Voltage-Gated Sodium Channel | NAV1.6 Voltage-Gated Sodium Channel | Nerve Tissue Proteins | Ranvier's Nodes | Sodium Channels | Spiral Ganglion

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Associated grants

  • Agency: NINDS NIH HHS, Id: R37 NS044916
  • Agency: NINDS NIH HHS, Id: R01 NS044916
  • Agency: NIMH NIH HHS, Id: R01 MH063503
  • Agency: NIDCD NIH HHS, Id: DC06387
  • Agency: NIMH NIH HHS, Id: MH063503
  • Agency: NINDS NIH HHS, Id: R01 NS029613
  • Agency: NIDCD NIH HHS, Id: R01 DC006387
  • Agency: NINDS NIH HHS, Id: NS044916
  • Agency: NINDS NIH HHS, Id: NS29613

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