The activation of glutamate receptors by kainic acid and domoic acid

✍ Scribed by David R. Hampson; Jerrie Lynn Manalo

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 56 KB
• Volume: 6
• Category: Article
• ISSN: 1056-9014
• DOI: 10.1002/(sici)1522-7189(199805/08)6:3/4<153::aid-nt16>3.0.co;2-1

✦ Synopsis

The neurotoxins kainic acid and domoic acid are potent agonists at the kainate and aamino-5-methyl-3-hydroxyisoxazolone-4-propionate (AMPA) subclasses of ionotropic glutamate receptors. Although it is well established that AMPA receptors mediate fast excitatory synaptic transmission at most excitatory synapses in the central nervous system, the role of the high af®nity kainate receptors in synaptic transmission and neurotoxicity is not entirely clear. Kainate and domoate differ from the natural transmitter, L-glutamate, in their mode of activation of glutamate receptors; glutamate elicits rapidly desensitizing responses while the two neurotoxins elicit non-desensitizing or slowly desensitizing responses at AMPA receptors and some kainate receptors. The inability to produce desensitizing currents and the high af®nity for AMPA and kainate receptors are undoubtedly important factors in kainate and domoate-mediated neurotoxicity. Mutagenesis studies on cloned glutamate receptors have provided insight into the molecular mechanisms responsible for these unique properties of kainate and domoate.