Distribution of K_v3 Subunits in Cochlear Afferent and Efferent Nerve Fibers Implies Distinct Role in Auditory Processing

Abstract

K v 3 family K + channels, by ensuring speedy repolarization of action potential, enable rapid and high frequency neuronal firing and high precision temporal coding of auditory information in various auditory synapses in the brain. Expression of different K v 3 subtypes within the auditory end organ has been reported. Yet, their precise role at the hair cell synaptic transmission has not been fully elucidated. Using immunolabeling and confocal microscopy we examined the expression pattern of different K v 3 family K + channel subunits in the nerve fibers innervating the cochlear hair cells. K v 3.1b was found in NKA-positive type 1 afferent fibers, exhibiting high signal intensity at the cell body, the unmyelinated dendritic segment, first heminode and nodes of Ranvier. K v 3.3 signal was detected in the cell body and the unmyelinated dendritic segment of NKA-positive type 1 afferent fibers but not in peripherin-positive type 2 afferent. K v 3.4 was found in ChAT-positive LOC and MOC efferent fibers as well as peripherin-positive type 2 afferent fibers. Such segregated expression pattern implies that each K v 3 subunits participate in different auditory tasks, for example, K v 3.1b and K v 3.3 in ascending signaling while K v 3.4 in feedback upon loud noise exposure.

Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse

“…Accurate transmission of AP timing was compromised in the Kv3.3KO, and the peak firing rate was reduced. Additionally, spontaneous AP firing was elevated (with respect to WT animals), likely reflecting hyper-excitability upstream in the auditory pathway, with Kv3.3 being expressed in spiral ganglion ( Kim et al, 2020 ) and the globular bushy cells ( Li et al, 2001 ; Cao et al, 2007 ) which give rise to the calyx of Held. The use of anesthetic for our in vivo study may affect auditory processing, but comparison with multiple other studies in mice and gerbil and using a range of different anesthetics showed that the synaptic delay measured in this study was favourably comparable to these other studies: ketamine/xylazine in mouse: 0.40ms ( Blosa et al, 2015 ), 0.46ms ( Kopp-Scheinpflug et al, 2003 ), 0.50ms ( Lorteije et al, 2009 ) ketamine/xylazine in gerbil: 0.44ms ( Tolnai et al, 2009 ).…”

“…Immunohistochemical studies have localized Kv3.3 subunits to many different synaptic terminals across the brain, from spiral ganglion afferent processes ( Kim et al, 2020 ), medial vestibular nuclei ( Brooke et al, 2010 ), cerebellar dentate nucleus ( Alonso-Espinaco et al, 2008 ), parallel fiber synapses ( Puente et al, 2010 ), posterior thalamic nucleus ( Chang et al, 2007 ), and the neuromuscular junction ( Brooke et al, 2004 ). It is interesting to consider why Kv3.3 is present at some synaptic terminals, but not all.…”

Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse

“…Accurate transmission of AP timing was compromised in the Kv3.3KO, and the peak firing rate was reduced. Additionally, spontaneous AP firing was elevated (with respect to WT animals), likely reflecting hyper-excitability upstream in the auditory pathway, with Kv3.3 being expressed in spiral ganglion (Kim et al , 2020) and the globular bushy cells (Li et al , 2001; Cao et al , 2007) (which give rise to the calyx of Held). The increased temporal jitter and AP delay further undermine interaural level discrimination (ILD) by reducing the gain and signal to noise and likely account for the impairment of sound localization in human spinocerebellar ataxia type 13 (SCA13) (Middlebrooks et al , 2013).…”

“…Immunohistochemical studies have localized Kv3.3 subunits to many different synaptic terminals across the brain, from spiral ganglion afferent processes (Kim et al , 2020), medial vestibular nuclei (Brooke et al , 2010), cerebellar dentate nucleus (Alonso-Espinaco et al , 2008), parallel fibre synapses (Puente et al , 2010), posterior thalamic nucleus (Chang et al , 2007b) and the neuromuscular junction (Brooke et al , 2004). The current study suggests that mutations associated with Kv3.3 such as SCA13, cause a range of neurological defects some of which will reflect aberrant neurotransmitter release.…”

Low-voltage Activating K+ Channels in Cochlear Afferent Nerve Fiber Dendrites

“…The methods for cochlear tissue preparation and imaging was adapted from the procedure described previously [23,24]. Cochleae were quickly collected from postnatal (P9, P15-21) Sprague Dawley rats and immediately perfused through either the oval or round windows with ice cold paraformaldehyde (4%) or formaldehyde (4%) prepared in phosphate buffered saline (PBS; pH 7.4).…”