Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca 2+ -permeable AMPA receptors
Proceedings of the National Academy of Sciences(2020)
摘要
Significance Noise can cause excitotoxic trauma to cochlear synapses by triggering excessive release of the neurotransmitter glutamate from the auditory sensory hair cells. We report that a specific class of glutamate receptors, Ca 2+ -permeable α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (CP-AMPARs), is largely responsible for this trauma. Because cochlear synapses are heterogenous with respect to glutamate receptors, the observation that a specific class is responsible might explain the variability in susceptibility to noise among synapses. Selective blockade of CP-AMPARs prevents excitotoxicity and noise-induced cochlear synaptopathy, while other glutamate receptors continue to mediate neurotransmission and allow hearing.
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