Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
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 rem...
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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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Online Access: | https://elifesciences.org/articles/52160 |
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author | Travis A Babola Calvin J Kersbergen Han Chin Wang Dwight E Bergles |
author_facet | Travis A Babola Calvin J Kersbergen Han Chin Wang Dwight E Bergles |
author_sort | Travis A Babola |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-10T04:39:12Z |
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id | doaj.art-fba236a8e3b7490197f0b91cd05f6f9e |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-12-10T04:39:12Z |
publishDate | 2020-01-01 |
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series | eLife |
spelling | doaj.art-fba236a8e3b7490197f0b91cd05f6f9e2022-12-22T02:01:56ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.52160Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular spaceTravis A Babola0https://orcid.org/0000-0003-4440-5029Calvin J Kersbergen1Han Chin Wang2Dwight E Bergles3https://orcid.org/0000-0002-7133-7378The Solomon Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United StatesThe Solomon Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United StatesThe Solomon Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United StatesThe Solomon Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, United States; Department of Otolaryngology Head and Neck Surgery, Johns Hopkins University, Baltimore, United States; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, United StatesNeurons 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.https://elifesciences.org/articles/52160cochleapurinergiccalciumhair cellP2Y1potassium |
spellingShingle | Travis A Babola Calvin J Kersbergen Han Chin Wang Dwight E Bergles Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space eLife cochlea purinergic calcium hair cell P2Y1 potassium |
title | Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space |
title_full | Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space |
title_fullStr | Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space |
title_full_unstemmed | Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space |
title_short | Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space |
title_sort | purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space |
topic | cochlea purinergic calcium hair cell P2Y1 potassium |
url | https://elifesciences.org/articles/52160 |
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