title: The effects of L-glutamate, AMPA, quisqualate, and kainate on retinal horizontal cells depend on adaptational state: implications for rod-cone interactions.
abstract: We studied the responses of isolated and intact luminosity-type horizontal cells (L-HC) in the Xenopus retina to L-glutamate (L-glu) and its analogs. Isolated L-HCs studied with whole-cell patch clamp responded to L-glu, kainate (KA), AMPA, or quisqualate (quis) with inward currents from a holding potential of -60 mV, associated with a conductance increase. The current elicited by KA was relatively large and sustained, whereas AMPA or quis evoked a desensitizing current. Coapplication of quis and KA resulted in a smaller current and conductance change than that evoked by a pulse of either alone at the same concentration. This finding suggests that the L-HC has a single subtype of glutamate receptor that responds to both quis and KA. Prior exposure to dopamine enhanced the KA-evoked current about twofold. In the superfused eyecup we found that L-HC responses to quinoxalinediones (CNQX or DNQX) and to L-glu, KA, AMPA, and quis varied as a function of adaptational state. When driven exclusively by either cones or by rods, CNQX/DNQX hyperpolarized the L-HC and reduced its light response, without altering response kinetics, indicating that both rods and cones communicate with L-HCs at ionotropic glutamatergic synapses. Under mesopic conditions, however, as CNQX or DNQX reduced cone input, the rod input to the L-HC increased up to fivefold in magnitude and had slowed kinetics. The depolarizing response of the L-HC to L-glu, AMPA, or quis was relatively small and transient under photopic conditions, but was much larger and sustained when the eyecup was dark adapted. The D1 dopamine antagonist SCH 23390 potentiated the response to quis. In contrast, responses to KA were largest in light-adapted eyecups, were potentiated by a D1 dopamine agonist, SKF 38393, and were reduced by SCH 23390. We hypothesize that the segregated populations of glutamate receptors in the L-HC opposite cone and rod synaptic endings can be separately modulated to respond differentially to the native transmitter, glutamate. In photopic and mesopic states the dominant cone input tonically inhibits rod to L-HC communication. This inhibition appears to occur at the postsynaptic membrane and may be mediated by second messengers.
authors.affiliation: Department of Physiology and Biophysics, New York University Medical Center, New York 10016.
authors.forename: D
authors.initials: D
authors.lastname: Krizaj
authors.forename: A
authors.initials: A
authors.lastname: Akopian
authors.forename: P
authors.initials: P
authors.lastname: Witkovsky
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000222:Adaptation, Physiological; D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D004553:Electric Conductivity; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008027:Light; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D011810:Quinoxalines; C056723:FG 9041; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D007608:Kainic Acid; D004298:Dopamine