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

AMPA-Preferring Receptors Mediate Excitatory Synaptic Inputs to Retinal Ganglion Cells Abstract 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 α-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-, γ-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 IC 50 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 IC 50 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. Footnotes Address for reprint requests: P. D. Lukasiewicz, Dept. of Ophthalmology and Visual Sciences, Campus Box 8096, Washington University School of Medicine, St. Louis, MO 63110-1093. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurophysiology The American Physiological Society

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

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The American Physiological Society
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Copyright © 2011 the American Physiological Society
ISSN
0022-3077
eISSN
1522-1598
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Abstract

Abstract 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 α-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-, γ-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 IC 50 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 IC 50 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. Footnotes Address for reprint requests: P. D. Lukasiewicz, Dept. of Ophthalmology and Visual Sciences, Campus Box 8096, Washington University School of Medicine, St. Louis, MO 63110-1093.

Journal

Journal of NeurophysiologyThe American Physiological Society

Published: Jan 1, 1997

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