sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice

Authors

Daniël O.J. Reijntjes, University Medical center Groningen
Jeong Han Lee, School of Medicine, University of Nevada Reno
seojin Park, School of Medicine, University of Nevada Reno
Nick M.A. Schubert, University Medical center Groningen
Marcel van Tuinen, University Medical center Groningen
Sarath Vijayakumar, University of Nebraska-LincolnFollow
Timothy A. Jones, University of Nebraska - LincolnFollow
Sherri M. Jones, University of Nebraska-LincolnFollow
Michael Anne Gratton, Washington University School of Medicine
Xiao-Ming Xia, Washington University School of Medicine
Ebenezer N. Yamoah, School of Medicine, University of Nevada Reno
Sonja J. Pyott, University Medical center GroningenFollow

ORCID IDs

http://orcid.org/0000-0002-6485-588X

http://orcid.org/0000-0003-3611-2939

Document Type

Article

Date of this Version

2-22-2019

Citation

The Author(s) 2019

Comments

(2019) 9:2573 | https://doi.org/10.1038/s41598-019-39119-z

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.