AMPA-PREFERRING RECEPTORS MEDIATE EXCITATORY SYNAPTIC INPUTS TO RETINAL
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-
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