Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca 2+ -permeable AMPA receptors
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 03, 2020
- Source ID
- 10.1073/pnas.1914247117
Entities
People
- Mark A. Rutherford
- Ning Hu
- Steven H Green
Organizations
- American Hearing Research Foundation
- Congressionally Directed Medical Research Programs
- National Institute on Deafness and Other Communication Disorders
- University of Iowa
- Washington University in St. Louis