title: AMPA receptor kinetics limit retinal amacrine cell excitatory synaptic responses.
abstract: Amacrine cells that respond transiently to maintained illumination are thought to mediate transient inhibitory input to ganglion cells. The excitation of these transient amacrine cells is thought to be limited by inhibitory feedback to bipolar cells. We investigated the possibility that desensitizing AMPA and/or kainate (KA) receptors on amacrine cells might also limit the duration of amacrine cell excitation. To determine how these receptors might affect amacrine cell input and output, we made whole-cell recordings from amacrine and ganglion cells in the salamander retinal slice. The specific AMPA receptor antagonist GYKI-53655 blocked non-NMDA receptor-mediated amacrine cell excitatory postsynaptic currents (EPSCs) and kainate puff-elicited currents, indicating that AMPA, and not KA, receptors mediated the responses. Cyclothiazide, an agent that reduces AMPA receptor desensitization, increased the amplitude and duration of amacrine cell EPSCs. To measure the output of transient amacrine cells, we recorded glycinergic inhibitory postsynaptic currents (IPSCs) from ganglion cells, and found that these were also enhanced by cyclothiazide. Thus, prolongation of amacrine cell AMPA receptor activation enhanced amacrine cell output. Current responses elicited by puffing glycine onto ganglion cell dendrites were not affected by cyclothiazide, indicating that the enhancement of glycinergic IPSCs was not due to a direct effect on glycine receptors. These data suggest that rapid AMPA receptor desensitization and/or deactivation limits glycinergic amacrine cell excitation and the resulting inhibitory synaptic output.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Tran
authors.forename: M H
authors.initials: MH
authors.lastname: Higgs
authors.forename: P D
authors.initials: PD
authors.lastname: Lukasiewicz
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001581:Benzothiadiazines / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism; D014562:Caudata / Q000033:anatomy & histology / Q000502:physiology*
chemical_list: D001581:Benzothiadiazines; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D001569:Benzodiazepines; C079692:GYKI 53655; C004639:cyclothiazide; D005998:Glycine