@article{c7876b12293642c996e94cd4b3577f1d,
title = "Compartmentalization of antagonistic Ca2+ signals in developing cochlear hair cells",
abstract = "During a critical developmental period, cochlear inner hair cells (IHCs) exhibit sensory-independent activity, featuring action potentials in which Ca2+ ions play a fundamental role in driving both spiking and glutamate release onto synapses with afferent auditory neurons. This spontaneous activity is controlled by a cholinergic input to the IHC, activating a specialized nicotinic receptor with high Ca2+ permeability, and coupled to the activation of hyperpolarizing SK channels. The mechanisms underlying distinct excitatory and inhibitory Ca2+ roles within a small, compact IHC are unknown. Making use of Ca2+ imaging, afferent auditory bouton recordings, and electron microscopy, the present work shows that unusually high intracellular Ca2+ buffering and {"}subsynaptic{"} cisterns provide efficient compartmentalization and tight control of cholinergic Ca2+ signals. Thus, synaptic efferent Ca2+ spillover and cross-talk are prevented, and the cholinergic input preserves its inhibitory signature to ensure normal development of the auditory system.",
keywords = "Calcium, Cochlea, Hair cells, Synaptic transmission",
author = "Moglie, {Marcelo J.} and Fuchs, {Paul A.} and Elgoyhen, {Ana Bel{\'e}n} and Goutman, {Juan D.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Michael J. Caterina for providing access to the swept-field confocal microscope (supported by the Neurosurgery Pain Research Institute at Johns Hopkins), David Zenisek for the gift of the RIBEYE-binding peptide, Carlos Valverde for providing valuable reagents and John Dempster for WinWCP software. We also thank Claudia Gatto and Nicol{\'a}s Gilio for excellent technical assistance and R{\'e}gis Nouvian for advice on perforated-patch recordings. This study was funded by Proyecto de Inves-tigaci{\'o}n Cient{\'i}fica y Tecnol{\'o}gica (PICT) Grant 2016-2155 (to J.D.G.), PICT Grant 2015-0919 (to A.B.E.), National Institute on Deafness and Other Communication Disorders Grants R01 DC001508 (to P.A.F. and A.B.E.) and R01 DC015309 (to P.A.F.), and Firca-NIH Grant 1R03TW009403-01 [to J.D.G. and Elisabeth Glowatzki (principal investigator)]. M.J.M. is the recipient of a “Bec.Ar” Presidential fellowship supported by the Argentinian government. Publisher Copyright: {\textcopyright} 2018 National Academy of Sciences. All Rights Reserved.",
year = "2018",
month = feb,
day = "27",
doi = "10.1073/pnas.1719077115",
language = "English (US)",
volume = "115",
pages = "E2095--E2104",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "9",
}