The coupling between Ca2+ channels and the exocytotic Ca2+ sensor at hair cell ribbon synapses varies tonotopically along the mature cochlea

Stuart L. Johnson, Jennifer Olt, Soyoun Cho, Henrique von Gersdorff, Walter Marcotti

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The cochlea processes auditory signals over a wide range of frequencies and intensities. However, the transfer characteristics at hair cell ribbon synapses are still poorly understood at different frequency locations along the cochlea. Using recordings from mature gerbils, we report here a surprisingly strong block of exocytosis by the slow Ca2+ buffer EGTA (10 mM) in basal hair cells tuned to high frequencies (~30 kHz). In addition, using recordings from gerbil, mouse, and bullfrog auditory organs, we find that the spatial coupling between Ca2+influx and exocytosis changes from nanodomain in low-frequency tuned hair cells (~<2 kHz) to progressively more microdomain in high-frequency cells (~>2 kHz). Hair cell synapses have thus developed remarkable frequency-dependent tuning of exocytosis: accurate low-latency encoding of onset and offset of sound intensity in the cochlea’s base and submillisecond encoding of membrane receptor potential fluctuations in the apex for precise phase-locking to sound signals. We also found that synaptic vesicle pool recovery from depletion was sensitive to high concentrations of EGTA, suggesting that intracellular Ca2+ buffers play an important role in vesicle recruitment in both low- and high-frequency hair cells. In conclusion, our results indicate that microdomain coupling is important for exocytosis in high-frequency hair cells, suggesting a novel hypothesis for why these cells are more susceptible to sound-induced damage than low-frequency cells; high-frequency inner hair cells must have a low Ca2+ buffer capacity to sustain exocytosis, thus making them more prone to Ca2+-induced cytotoxicity.

Original languageEnglish (US)
Pages (from-to)2471-2484
Number of pages14
JournalJournal of Neuroscience
Volume37
Issue number9
DOIs
StatePublished - Mar 1 2017

Keywords

  • Calcium channels
  • Cochlea
  • Exocytosis
  • Hair cells
  • Ribbon synapse

ASJC Scopus subject areas

  • Neuroscience(all)

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