title: Quisqualate, kainate and NMDA can initiate spreading depression in the turtle cerebellum.
abstract: This study evaluated the role of excitatory amino acid (EAA) receptor activation in spreading depression (SD), using the in vitro turtle cerebellum as a model system. SD was triggered by electrical stimulation or by elevated K+ after the cerebellum had been conditioned for at least 30 min with physiological saline in which most of the chloride had been replaced by propionate. SD was recognized as a transient (1-3 min) negative shift of extracellular potential accompanied by depression of evoked potentials (15-30 min) and an increase of extracellular K+ up to 60 mM, which spread across the cerebellum at rates of 1-7 mm/min. SD usually commenced in the granular layer, which apparently contains the 3 major EAA receptor subtypes, quisqualate, kainate and N-methyl-D-aspartate (NMDA), then subsequently spread to the molecular layer, which is largely free of NMDA receptors. Glutamate, aspartate, NMDA, kainate and quisqualate all triggered SD. Kynurenic acid and 2-aminophosphonovaleric acid (APV) inhibited SD under certain conditions further suggesting involvement of EAA receptors. The initiation of SD was blocked by high Mg2+ and facilitated in low extracellular Mg2+, which also eliminated the delay in molecular layer SD onset. Our data suggest that no one EAA receptor subtype is singly responsible for SD.
authors.affiliation: Department of Physiology and Biophysics, New York University Medical Center, NY 10016.
authors.forename: M
authors.initials: M
authors.lastname: Lauritzen
authors.forename: M E
authors.initials: ME
authors.lastname: Rice
authors.forename: Y
authors.initials: Y
authors.lastname: Okada
authors.forename: C
authors.initials: C
authors.lastname: Nicholson
mesh_terms: D015763:2-Amino-5-phosphonovalerate; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate; D009433:Neural Inhibition / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D014426:Turtles / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D010069:Oxadiazoles; D001224:Aspartic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D014633:Valine; D008274:Magnesium; D007608:Kainic Acid