Excitatory amino acid antagonists protect cochlear auditory neurons from excitotoxicity.

Abstract

Since ischemic damage in the brain is linked to glutamate excitotoxicity, the effects of an acute exposure to glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) or N-methyl-D aspartate (NMDA) on the radial dendrites were compared with those occurring after a severe cochlear ischemia. Glutamate and AMPA, but not NMDA, produced a drastic swelling restricted to the radial dendrites below the inner hair cells (IHCs). At a concentration of 20 microM AMPA, a full electrophysiological recovery could be observed in some cochleas after washing the drug out. A prior perfusion of 6-7-dinitroquinoxaline-2,3-dione (DNQX, 50 microM) prevented the 25 microM AMPA-induced dendritic swelling. No protective effect of D-2-amino-5-phosphonopentanoate (D-AP5) could be observed. In the same way, ischemia (5-40 minutes) resulted in a clear swelling of the radial dendrites. While D-AP5 had no protective effects, 50 microM DNQX protected most of the radial dendrites from the ischemia-induced swelling, excepting those contacting the modiolar side of the IHCs. Finally, 50 microM DNQX + 50 microM D-AP5 resulted in a nearly complete protection of all the radial dendrites. Altogether, these results suggest that the acute swelling of radial dendrites primarily occurs via AMPA/kainate receptors. However, in radial dendrites contacting the inner hair cells on their modiolar side, NMDA receptors may be also involved.

• Authors: J L Puel, R Pujol, F Tribillac, S Ladrech, M Eybalin
• Journal: The Journal of comparative neurology (J Comp Neurol) Vol. 341 Issue 2 Pg. 241-56 (Mar 08 1994) ISSN: 0021-9967 [Print] United States
• PMID: 7512999 (Publication Type: Journal Article)

Chemical References

• Amino Acids
• Excitatory Amino Acid Antagonists
• Glutamates
• Neurotransmitter Agents
• Quinoxalines
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• Glutamic Acid
• FG 9041
• N-Methylaspartate
• 2-Amino-5-phosphonovalerate
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Topics

• 2-Amino-5-phosphonovalerate (pharmacology)
• Amino Acids (antagonists & inhibitors, toxicity)
• Animals
• Brain Ischemia (pathology, physiopathology)
• Cochlea (cytology, drug effects, pathology)
• Cochlear Microphonic Potentials (drug effects)
• Dendrites (drug effects, ultrastructure)
• Electrophysiology
• Excitatory Amino Acid Antagonists
• Female
• Glutamates (toxicity)
• Glutamic Acid
• Guinea Pigs
• Hair Cells, Auditory, Inner (drug effects)
• Male
• N-Methylaspartate (antagonists & inhibitors, toxicity)
• Neurons, Afferent (drug effects)
• Neurotransmitter Agents (antagonists & inhibitors, toxicity)
• Perfusion
• Quinoxalines (pharmacology)
• Receptors, AMPA (antagonists & inhibitors, drug effects)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, drug effects)
• alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (antagonists & inhibitors, toxicity)