Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
- Johns Hopkins University School of Medicine, United States
Abstract
Neurons in developing sensory pathways exhibit spontaneous bursts of electrical activity that are critical for survival, maturation and circuit refinement. In the auditory system, intrinsically generated activity arises within the cochlea, but the molecular mechanisms that initiate this activity remain poorly understood. We show that burst firing of mouse inner hair cells prior to hearing onset requires P2RY1 autoreceptors expressed by inner supporting cells. P2RY1 activation triggers K+ efflux and depolarization of hair cells, as well as osmotic shrinkage of supporting cells that dramatically increased the extracellular space and speed of K+ redistribution. Pharmacological inhibition or genetic disruption of P2RY1 suppressed neuronal burst firing by reducing K+ release, but unexpectedly enhanced their tonic firing, as water resorption by supporting cells reduced the extracellular space, leading to K+ accumulation. These studies indicate that purinergic signaling in supporting cells regulates hair cell excitability by controlling the volume of the extracellular space.
Data availability
All data generated or analyzed in this study are included in the manuscript. Source code for analysis and figure generation are located at: https://github.com/tbabola/P2ry1_eLife_SourceCode
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Gene Expression by Mouse Inner Ear Hair Cells During DevelopmentNCBI Gene Expression Omnibus, GSE60019.
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (DC016497)
- Travis A Babola
National Institute on Deafness and Other Communication Disorders (DC008860)
- Dwight E Bergles
National Institute of Neurological Disorders and Stroke (NS091018)
- Travis A Babola
National Institute on Deafness and Other Communication Disorders (DC000023)
- Travis A Babola
Brain Science Institute, Johns Hopkins University
- Dwight E Bergles
Rubenstein Fund for Hearing Research
- Dwight E Bergles
Otonomy, Inc
- Dwight E Bergles
National Institute of Neurological Disorders and Stroke (NS050274)
- Dwight E Bergles
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in accordance with the recommendations provided in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments and procedures were approved by the Johns Hopkins Institutional Care and Use Committee (protocol M018M330). All surgery was performed under isoflurane anesthesia and every effort was made to minimize suffering.
Copyright
© 2020, Babola et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
eLife 9:e52160.
https://doi.org/10.7554/eLife.52160
