AMPA-PREFERRING RECEPTORS MEDIATE EXCITATORY SYNAPTIC INPUTS TO RETINAL GANGLION CELLS. Lukasiewicz, Peter D., James A. Wilson and Jean E. Lawrence. Department of Ophthalmology & Visual Sciences and Department of Anatomy & Neurobiology. Washington University School of Medicine, St. Louis, MO 63110- 1093.
APStracts 3:0205N, 1996.
Pharmacological studies were performed to determine whether [alpha]-amino-3 hydroxy-5-methyl-4-isoazoleprionic acid (AMPA)- and/or kainate (KA)-preferring receptors mediate excitatory synaptic inputs to tiger salamander retinal ganglion cells. Excitatory postsynaptic currents (EPSCs), evoked either by light or by stimulating bipolar cells with puffs of K + , were measured using whole-cell recording techniques in the tiger salamander retinal slice preparation. The AMPA/KA component of the EPSCs was isolated by including antagonists of glycine-, GABA- and NMDA-receptors in the bath. The AMPA- preferring receptor antagonists, GYKI-52466 and GYKI-53665, reduced light- evoked EPSCs and K + puff-evoked EPSCs amplitudes in a concentration-dependent manner. The IC 50 values for GYKI-52466 were 3.6[mu]M and 4.2[mu]M for the light- and puff-evoked responses, respectively. The more potent GYKI-53665 had IC 50 values of 0.7 [mu]M for both the light- and puff evoked responses. Kainate activates both KA- and AMPA-preferring receptors. Kainate-evoked currents were completely blocked 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 KA-preferring receptors, did not enhance either EPSCs or glutamate-evoked responses. By contrast, cyclothiazide, which selectively enhances AMPA-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.

Received 5 April 1996; accepted in final form 5 September 1996.
APS Manuscript Number J282-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996