Desensitizing glutamate receptors shape excitatory synaptic inputs to tiger salamander retinal ganglion cells.
AMPA/kainate (KA) receptors mediate a component of ganglion cell excitatory postsynaptic currents (EPSCs). We investigated whether desensitization at these receptors contribute to the shape of transient EPSCs in ON-OFF ganglion cells. Whole-cell, voltage-clamp recordings were made from ganglion cells in the retinal slice or in isolation. EPSCs were evoked by either stimulating the slice with light or puffing K+ at the outer plexiform layer (OPL). The AMPA/KA receptor-mediated component of the EPSCs was isolated by including NMDA receptor antagonists in the bath. Strychnine and picrotoxin blocked inhibitory inputs. In isolated ganglion cells, cyclothiazide (10 microM), which blocks desensitization in non-NMDA receptors, enhanced both the amplitude and the duration of currents evoked by puffs of AMPA or glutamate. EPSCs evoked by K(+)-puffs in the OPL were also enhanced by cyclothiazide (30 microM). When AMPA/KA receptors were blocked with NBQX (10 microM), no enhancement of the EPSCs by cyclothiazide was observed, indicating that cyclothiazide did not act presynaptically. Cyclothiazide also enhanced the amplitude and duration of both the ON and OFF light-evoked (L-) EPSCs recorded in ON-OFF ganglion cells. Current-voltage relationships showed the enhancement was not voltage dependent. When control and enhanced responses where normalized, it was observed that the rate of desensitization of both the ON and OFF L-EPSCs was decreased by cyclothiazide. Cyclothiazide selectively enhanced the AMPA/KA receptor-mediated component of ganglion cells EPSCs, suggesting that desensitization of AMPA/KA receptors shape transient L-EPSCs.
Lukasiewicz
P D
PD
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Lawrence
J E
JE
Valentino
T L
TL
D000557:Ambystoma; D000818:Animals; D001581:Benzothiadiazines / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004594:Electrophysiology; D005971:Glutamates; D008027:Light; D018091:Receptors, AMPA / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D001581:Benzothiadiazines; D003981:Diazoxide; D005971:Glutamates; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; C004639:cyclothiazide