The Coupling between Ca2+Channels and the Exocytotic Ca2+Sensor at Hair Cell Ribbon Synapses Varies Tonotopically along the Mature Cochlea.
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.SIGNIFICANCE STATEMENTIn the inner ear, sensory hair cells signal reception of sound. They do this by converting the sound-induced movement of their hair bundles present at the top of these cells, into an electrical current. This current depolarizes the hair cell and triggers the calcium-induced release of the neurotransmitter glutamate that activates the postsynaptic auditory fibers. The speed and precision of this process enables the brain to perceive the vital components of sound, such as frequency and intensity. We show that the coupling strength between calcium channels and the exocytosis calcium sensor at inner hair cell synapses changes along the mammalian cochlea such that the timing and/or intensity of sound is encoded with high precision.
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Stuart L
0000-0003-3355-650X
SL
Johnson
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Jennifer
0000-0002-5380-8826
J
Olt
Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, and.|Center for Sensory Neuroscience, Boys Town National Research Hospital, Omaha, Nebraska 68131.
Soyoun
S
Cho
Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, and w.marcotti@sheffield.ac.uk vongersd@ohsu.edu.
Henrique
0000-0002-4404-3307
H
von Gersdorff
Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom, w.marcotti@sheffield.ac.uk vongersd@ohsu.edu.
Walter
0000-0002-8770-7628
W
Marcotti
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D065096:Calcium Chelating Agents / Q000494:pharmacology; D003051:Cochlea / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005089:Exocytosis / Q000502:physiology*; D005260:Female; D005849:Gerbillinae; D006198:Hair Cells, Auditory / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D011892:Rana catesbeiana; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology
D020746:Calcium Channels, L-Type; D065096:Calcium Chelating Agents; D004533:Egtazic Acid; D002118:Calcium
calcium channels; cochlea; exocytosis; hair cells; ribbon synapse