Purinergic signaling in cochlear supporting cells reduces hair cell excitability by increasing the extracellular space
Year: 2020
Type: article
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, slowing K + clearance. These studies indicate that purinergic signaling in supporting cells regulates hair cell excitability by controlling the volume of the extracellular space.
Source: eLife
DOI: 10.7554/elife.52160
Institution: Johns Hopkins University
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: G1786445697, Medical Scientist Training Program, G2435101893, G2815552965, G285241203, G3974443412, JHU Center for Neuroscience Research, Supporting-cell control of inner hair cell excitability through purinergic signaling, G8121226415, G9000010266, Training Program in Neuroscience, G9000121389, Trainging Program in Hearing and Balance, Spontaneous activity in the developing auditory system, Medical Scientist Training Program
OpenAlex ID: W2998939305
