ATP-induced Ca2+ release in cochlear outer hair cells: Localization of an inositol triphosphate-gated Ca2+ store to the base of the sensory hair bundle

Fabio Mammano, Gregory I. Frolenkov, Laura Lagostena, Inna A. Belyantseva, Mauricio Kurc, Valerie Dodane, Alberto Colavita, Bechara Kachar

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

We used a high-performance fluorescence imaging system to visualize rapid changes in intracellular free Ca2+ concentration ([Ca2+](l)) evoked by focal applications of extracellular ATP to the hair bundle of outer hair cells (OHCs): the sensory-motor receptors of the cochlea. Simultaneous recordings of the whole-cell current and Calcium Green-1 fluorescence showed a two-component increase in [Ca2+](i). After an initial entry of Ca2+ through the apical membrane, a second and larger, inositol triphosphate (InsP3)-gated, [Ca2+](i) surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca2+ release site showed that it coincides with the localization of a unique system of endoplasmic reticulum (ER) membranes and mitochondria known as Hensen's body. Using confocal immunofluorescence microscopy, we showed that InsP3 receptors share this location. Consistent with a Ca2+-mobilizing second messenger system linked to ATP-P2 receptors, we also determined that an isoform of G-proteins is present in the stereocilia. Voltage-driven cell shape changes and nonlinear capacitance were monitored before and after ATP application, showing that the ATP-evoked [Ca2+](i) rise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca2+- clearance power of the stereocilia and transiently elevates [Ca2+](i) at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and potentially influence mechanotransduction.

Original languageEnglish
Pages (from-to)6918-6929
Number of pages12
JournalJournal of Neuroscience
Volume19
Issue number16
DOIs
StatePublished - Aug 15 1999

Keywords

  • Calcium imaging
  • Cochlea
  • Electromotility
  • Endoplasmic reticulum
  • G-proteins
  • Hensen's body
  • InsP
  • Mitochondria
  • Organ of Corti
  • Patch-clamp
  • Purinergic receptors
  • Sensory transduction

ASJC Scopus subject areas

  • General Neuroscience

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