Abstract
Potassium (K+) channels shape the response properties of neurons. Although enormous progress has been made to characterize K+ channels in the primary auditory neurons, the molecular identities of many of these channels and their contributions to hearing in vivo remain unknown. Using a combination of RNA sequencing and single molecule fluorescent in situ hybridization, we localized expression of transcripts encoding the sodium-activated potassium channels KNa1.1 (SLO2.2/Slack) and KNa1.2 (SLO2.1/Slick) to the primary auditory neurons (spiral ganglion neurons, SGNs). To examine the contribution of these channels to function of the SGNs in vivo, we measured auditory brainstem responses in KNa1.1/1.2 double knockout (DKO) mice. Although auditory brainstem response (wave I) thresholds were not altered, the amplitudes of suprathreshold responses were reduced in DKO mice. This reduction in amplitude occurred despite normal numbers and molecular architecture of the SGNs and their synapses with the inner hair cells. Patch clamp electrophysiology of SGNs isolated from DKO mice displayed altered membrane properties, including reduced action potential thresholds and amplitudes. These findings show that KNa1 channel activity is essential for normal cochlear function and suggest that early forms of hearing loss may result from physiological changes in the activity of the primary auditory neurons.
Highlights
Encoding of auditory signals in the cochlea by the primary auditory neurons, the spiral ganglion neurons (SGNs), requires a repertoire of ion channels to establish the variation in response properties that are essential for normal hearing
As part of a larger effort to identify the repertoire of ion channels that regulate encoding of auditory signals as part of the afferent signalling complex[3], we used RNA sequencing (RNAseq) to obtain whole transcriptomes from intact preparations of the organ of Corti and SGNs isolated from mice (Fig. 1)
To validate the utility of RNAseq to identify SLO transcripts in the sensorineural structures of the inner ear, we examined the expression of KNa1-encoding transcripts in other tissues collected in parallel
Summary
Encoding of auditory signals in the cochlea by the primary auditory neurons, the spiral ganglion neurons (SGNs), requires a repertoire of ion channels to establish the variation in response properties that are essential for normal hearing. Genetic deletion of either KNa1.119 or KNa1.220 results in increased excitability of distinct populations of dorsal root ganglion (DRG) neurons and exacerbated nociceptor responses These findings, expression of KNa channels in primary sensory neurons and contribution of KNa activity to signal encoding in the central auditory system, motivate examination of their role in regulating the function of the peripheral auditory system. We localized KNa1 transcript expression to the sensorineural structures of the inner ear and SGNs. We did not find evidence for expression of KCa5.1 in the SGNs. We took advantage of KNa1.1/1.2 double knockout (DKO) mice to identify the contribution of KNa1 channels to function of the SGNs in vivo and determine the response properties of isolated SGNs in vitro. This work highlights the utility of this experimental approach to inventory the ion channels that regulate encoding of auditory signals and identify their contributions to hearing
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