AMPA-preferring receptors mediate excitatory synaptic inputs to retinal ganglion cells

J Neurophysiol. 1997 Jan;77(1):57-64. doi: 10.1152/jn.1997.77.1.57.

Abstract

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 microM for the light- and puff-evoked responses, respectively. The more potent GYKI-53665 had IC50 values of 0.7 microM 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 microM 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ambystoma
  • Animals
  • Anti-Anxiety Agents*
  • Benzodiazepines / pharmacology
  • Dendrites / drug effects
  • Electrophysiology
  • Evoked Potentials, Visual / drug effects
  • Evoked Potentials, Visual / physiology
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Microelectrodes
  • Patch-Clamp Techniques
  • Photic Stimulation
  • Potassium / pharmacology
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / physiology*
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / physiology*
  • Stimulation, Chemical

Substances

  • Anti-Anxiety Agents
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • GYKI 53665
  • Receptors, AMPA
  • Receptors, Neurotransmitter
  • GYKI 52466
  • Benzodiazepines
  • Potassium