AMPA-PREFERRING RECEPTORS MEDIATE EXCITATORY SYNAPTIC INPUTS TO RETINAL GANGLION-CELLS

Pharmacological studies were performed to determine whether alpha-amin o-3-hydroxy-5-methyl-4-isoazoleprionic acid (AMPA)- and/or kainate (KA )-preferring receptors mediate excitatory synaptic inputs to tiger sal amander retinal ganglion cells. Excitatory postsynaptic currents (EPSC s), evoked either by light or by stimulating bipolar cells with puffs of K+, were measured using whole cell recording techniques in the tige r salamander retinal slice. The AMPA/KA component of the EPSCs was iso lated by including antagonists of glycine-, gamma-aminobutyric acid (G ABA)- and NMDA-receptors in the bath. The AMPA-preferring receptor ant agonists, -4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochlo ride (GYKI-52466) and 8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepi ne (GYKI-53665), reduced Light-evoked EPSCs and K+ puff-evoked EPSCs a mplitudes in a concentration-dependent manner. The IC50 values for GYK I-52466 were 3.6 and 4.2 mu M for the light- and puff-evoked responses , respectively. The more potent GYKI-53665 had IC50 values of 0.7 mu M for both the light- and puff evoked responses. KA activates both KA- and AMPA-preferring receptors. KA-evoked currents were completely bloc ked by 10-40 mu M GYKI-53665, indicating that little or no excitatory synaptic current was mediated by KA-preferring receptors. Concanavalin A, a compound that preferentially potentiates responses mediated by K A-preferring receptors, did not enhance either EPSCs or glutamate-evok ed responses. By contrast, cyclothiazide, which selectively enhances A MPA-preferring receptor mediated responses, was found to enhance both EPSCs and glutamate-evoked currents. Our results indicate that the non -NMDA component of ganglion cell EPSCs is mediated by AMPA-preferring receptors and not significantly by KA-preferring receptors.