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Uniquantal Release through a Dynamic Fusion Pore Is a Candidate Mechanism of Hair Cell Exocytosis

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Wolf,  Fred
Research Group Theoretical Neurophysics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;
Department of Nonlinear Dynamics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society;

Moser,  Tobias
Max Planck Society;

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Citation

Chapochnikov, N., Takago, H., Huang, C.-H., Pangrsic, T., Khimich, D., Neef, J., et al. (2014). Uniquantal Release through a Dynamic Fusion Pore Is a Candidate Mechanism of Hair Cell Exocytosis. Neuron, 83(6), 1389-1403. doi:10.1016/j.neuron.2014.08.003.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0029-0F05-8
Abstract
The mechanisms underlying the large amplitudes and heterogeneity of excitatory postsynaptic currents (EPSCs) at inner hair cell (IHC) ribbon synapses are unknown. Based on electrophysiology, electron and superresolution light microscopy, and modeling, we propose that uniquantal exocytosis shaped by a dynamic fusion pore is a candidate neurotransmitter release mechanism in IHCs. Modeling indicated that the extended postsynaptic AMPA receptor clusters enable large uniquantal EPSCs. Recorded multiphasic EPSCs were triggered by similar glutamate amounts as monophasic ones and were consistent with progressive vesicle emptying during pore flickering. The fraction of multiphasic EPSCs decreased in absence of Ca2+ influx and upon application of the Ca2+ channel modulator BayK8644. Our experiments and modeling did not support the two most popular multiquantal release interpretations of EPSC heterogeneity: (1) Ca2+-synchronized exocytosis of multiple vesicles and (2) compound exocytosis fueled by vesicle-to-vesicle fusion. We propose that IHC synapses efficiently use uniquantal glutamate release for achieving high information transmission rates.