Glutamate and kainate-induced currents of primate ganglion
cells were studied using the whole-cell patch-clamp technique
in a retinal slice preparation. Antagonists and allosteric
modulators of desensitization selective for either
α-amino-3-hydroxy-5-methyl-4-isoazoleprionic acid (AMPA)-
or kainate-preferring receptors were used to determine the
contributions of each type of receptor to excitatory responses.
With synaptic transmission and NMDA receptors blocked, the
AMPA-preferring receptor antagonist GYKI 52466 (30 μM–100
μM) reversibly blocked most of the glutamate-induced current
in ganglion cells. GYKI 52466 also blocked the response in ganglion
cells to focally applied kainate, suggesting that the current
response to kainate arises from activation of AMPA-preferring
receptors, and not kainate-preferring receptors. Both cyclothiazide
(10 μM–100 μM) and the novel drug
4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluoro-phenoxyacetamide
(PEPA, 20 μM–100 μM), which selectively enhance
responses mediated by AMPA-preferring receptors, enhanced
glutamate-induced responses of ganglion cells. Since these drugs
preferentially inhibit desensitization of the flip and flop
splice variants, respectively, of AMPA-preferring receptors,
it is likely that both splice variants are present on these
ganglion cells. Concanavalin A, which selectively suppresses
the desensitization of kainate-preferring receptors, had no
effect on the glutamate-induced responses of ganglion cells.
We conclude that the non-NMDA component of the excitatory,
glutamatergic input to primate ganglion cells is mediated largely
by AMPA-preferring receptors, with little, if any,
kainate-preferring receptor-mediated response.