Aspirin selectively augmented N-methyl-D-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice.
Aspirin is commonly used to study tinnitus in animal models because of its ability to induce tinnitus in human subjects. However, the mechanism by which aspirin affects auditory function remains unclear. To investigate the effect of aspirin on the cochlear neurotransmission, we studied its interactions with major types of membrane channels and receptors regulating the excitability of cultured type I spiral ganglion (SG) neurons. Results showed that aspirin had little effect on voltage-gated sodium and potassium currents of SG neurons. In contrast, it selectively potentiated the N-methyl-D-aspartate (NMDA) subtype of the glutamate responses in SG neurons while showing little effect on the alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid and kainate types of glutamate responses. The aspirin-induced current in the presence of NMDA increased in a dose-dependent manner with a half maximal concentration of 2.2 mM, and it was blocked by NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid or Mg(2+). These in vitro results suggested that aspirin could interfere with the glutamatergic neurotransmission in the cochlea by selectively amplifying NMDA-mediated responses.
Section on Neurobiology, Leslie & Susan Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 West Third Street, Los Angeles, CA 90057, USA.
Ben-Gang
BG
Peng
Shanping
S
Chen
Xi
X
Lin
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects / Q000502:physiology; D017470:Receptors, Glutamate / Q000187:drug effects; D013136:Spiral Ganglion / Q000187:drug effects* / Q000502:physiology*
D004338:Drug Combinations; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D017470:Receptors, Glutamate; D016202:N-Methylaspartate; D001241:Aspirin