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.