Compartmentalization of antagonistic Ca2+ signals in developing cochlear hair cells

Marcelo J. Moglie, Paul A. Fuchs, Ana Belén Elgoyhen, Juan D. Goutman

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)E2095-E2104
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number9
DOIs
StatePublished - Feb 27 2018

Keywords

  • Calcium
  • Cochlea
  • Hair cells
  • Synaptic transmission

ASJC Scopus subject areas

  • General

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