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J Neurophysiol 77: 57-64, 1997;
0022-3077/97 $5.00
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The Journal of Neurophysiology Vol. 77 No. 1 January 1997, pp. 57-64
Copyright ©1997 The American Physiological Society

AMPA-Preferring Receptors Mediate Excitatory Synaptic Inputs to Retinal Ganglion Cells

Peter D. Lukasiewicz, James A. Wilson, and Jean E. Lawrence

Departments of Ophthalmology and Visual Sciences and Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110-1093

Lukasiewicz, Peter D., James A. Wilson, and Jean E. Lawrence. AMPA-preferring receptors mediate excitatory synaptic inputs to retinal ganglion cells. J. Neurophysiol. 77: 57-64, 1997. 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. The AMPA/KA component of the EPSCs was isolated by including antagonists of glycine-, gamma -aminobutyric acid (GABA)- and NMDA-receptors in the bath. The AMPA-preferring receptor antagonists, 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI-52466) and 1-(4-aminophenyl)-3-methylcarbamyl - 4 - methyl - 7,8 - methylenedioxy - 3,4 - dihydro - 5H - 2,3 - benzodiazepine (GYKI-53665), reduced light-evoked EPSCs and K+ puff-evoked EPSCs amplitudes in a concentration-dependent manner. The IC50 values for GYKI-52466 were 3.6 and 4.2 µM for the light- and puff-evoked responses, respectively. The more potent GYKI-53665 had IC50 values of 0.7 µM for both the light- and puff evoked responses. KA activates both KA- and AMPA-preferring receptors. KA-evoked currents were completely blocked by 10-40 µM 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.




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