Maturation of Na_Vand K_VChannel Topographies in the Auditory Nerve Spike Initiator before and after Developmental Onset of Hearing Function

Abstract

Auditory nerve excitation and thus hearing depend on spike-generating ion channels and their placement along the axons of auditory nerve fibers (ANFs). The developmental expression patterns and native axonal locations of voltage-gated ion channels in ANFs are unknown. Therefore, we examined the development of heminodes and nodes of Ranvier in the peripheral axons of type I ANFs in the rat cochlea with immunohistochemistry and confocal microscopy. Nodal structures presumably supporting presensory spiking formed between postnatal days 5 (P5) and P7, including Ankyrin-G, Na V 1.6, and Caspr. These immature nodal structures lacked low-voltageactivated K V 1.1 which was not enriched at juxtaparanodes until approximately P13, concurrent with the developmental onset of acoustic hearing function. Anatomical alignment of ANF spike-initiating heminodes relative to excitatory input from inner hair cell (IHC) ribbon synapses continued until approximately P30. High-voltage-activated K V 3.1b and K V 2.2 were expressed in mutually exclusive domains: K V 3.1b was strictly localized to nodes and heminodes, whereas K V 2.2 expression began at the juxtaparanodes and continued centrally along the first internode. At spike-initiating heminodes in the distal osseous spiral lamina, Na V 1.1 partly overlapped Na V 1.6 and ankyrin-G. ANFs displayed K V 7.2 and K V 7.3 at heminodes, nodes, internodes, and the unmyelinated synaptic terminal segments beneath IHCs in the organ of Corti. In response to sound, spikes are initiated at the heminode, which is tightly coupled to the IHC ribbon synapse ϳ20 -40 m away. These results show that maturation of nodal alignment and ion channel content may underlie postnatal improvements of ANF excitability and discharge synchrony.

Postnatal maturation of auditory-nerve heterogeneity, as seen in spatial gradients of synapse morphology in the inner hair cell area

“…Regardless of how this discrepancy is ultimately resolved, the present study suggests that the fully mature relation between SR and threshold is not present in mouse until after P21. Similarly, a recent study of the topography of Na + and K + channel expression in the rat cochlear nerve reports continuing developmental changes post-synaptically until P30 (Kim et al, 2016). Thus, any gene expression study aimed at identifying the molecular differences among the different SR groups should be extracting RNA from animals at P28 or older.…”

Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance

“…This is most likely because Kv3.1b is targeted to the subcellular location that has the greatest impact on action potential generation: the axon initial segment (251). Along myelinated axons, Kv3.1b colocalizes with Na ϩ channels and with the adaptor protein ankyrin G at nodes and heminodes (50,123). In cortical and hippocampal interneurons, Kv3.1b is localized to the axon hillock, as well as to proximal dendrites, the soma, unmyelinated axonal membranes, and axon terminals (172,214).…”

Auditory Neuropathy Spectrum Disorders: From Diagnosis to Treatment: Literature Review and Case Reports

“…3), ankyrin-G and Caspr channels on the auditory fibers, also contribute to the accurate coupling of neural firing to the synaptic input [33]. From the synapse with IHCs, peripheral axons of SGNs proceed in the modiolus of the cochlea and continue as proximal axons towards the midbrain.…”