1681465

Quisqualate agonists occlude kainate-induced current in cultured striatal neurons.

Article date: 1991/1/1

PubMed ID: 1681465

Journal name: Neuroscience (ISSN: 0306-4522)

ABSTRACT

We employed the whole cell patch-clamp technique to examine the ionic currents induced via activation of kainate/quisqualate receptors on striatal neurons in primary culture when N-methyl-D-aspartate receptors were blocked by selective antagonists. Bath perfusion of 10 microM-1 mM each of quisqualate, glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (a selective quisqualate agonist) or kainate, induced only a sustained current, but more rapid application by pressure ejection of each of the first three agonists (but not kainate) also activated a rapidly desensitizing current. The current induced by a near-saturating concentration of kainate (1 mM) was, on average, 16-fold larger than the maximum sustained current induced by quisqualate (10 microM), or 7.5-fold larger than that induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (100 microM) or glutamate (100 microM). When kainate (100 microM-10 mM) was co-applied with each of the agonists (1 microM-1 mM), the sustained current was not the algebraic sum of the currents activated by kainate or the other agonist alone; rather, the kainate-induced current was increasingly occluded by co-application with increasing concentrations of another agonist. The potency to occlude kainate-induced current had a rank order of quisqualate greater than alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate approximately glutamate; although at sufficiently high concentrations all three agonists could occlude the kainate-induced current completely. When kainate and quisqualate were co-applied during the continued presence of quisqualate, the onset of the kainate-induced sustained current was dramatically slowed. However, the steady-state occlusion by quisqualate could be abolished when the ratio kainate to quisqualate was raised to 100:1; therefore, the occlusion appears to involve a competition between kainate and quisqualate at some shared receptor binding sites which have a higher affinity for quisqualate than kainate.

Author List: Tse F W, Weiss S, MacVicar B A

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Amino Acids; Glutamates; Ibotenic Acid; Glutamic Acid; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Quisqualic Acid; Kainic Acid;

Mesh terms: Amino Acids/physiology; Animals; Cells, Cultured; Corpus Striatum/cytology; Drug Interactions; Electrophysiology; Glutamates/pharmacology; Glutamic Acid; Ibotenic Acid/analogs & derivatives; Kainic Acid/pharmacology; Neurons/physiology; Quisqualic Acid/pharmacology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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