Quisqualate agonists occlude kainate-induced current in cultured striatal neurons.
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.
Department of Medical Physiology, University of Calgary, Faculty of Medicine, Alberta, Canada.
F W
FW
Tse
S
S
Weiss
B A
BA
MacVicar
D000596:Amino Acids / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D004347:Drug Interactions; D004594:Electrophysiology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D016318:Quisqualic Acid / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D005971:Glutamates; D007051:Ibotenic Acid; D018698:Glutamic Acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid