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Division of Neuroscience, Children's Hospital, Boston, MA.

1. The pharmacological properties of excitatory amino acid responses on ganglion cells dissociated from the rat retina were examined with the use of the whole-cell voltage-clamp technique. 2. L-Glutamate at a concentration of 50 microM produced inward non-desensitizing currents at negative holding potentials in nearly every cell tested (83%, n = 18) In physiological solutions, L-glutamate responses reversed at approximately -9 mV, and higher concentrations of this agonist introduced a desensitizing component to the response. 3. At negative holding potentials, kainate (25-125 microM) produced inward currents in all of the cells tested (n = 37). These currents never desensitized, even at high agonist concentrations, and reversed near -6 mV. Currents induced by 50 microM-kainate were reversibly antagonized by kynurenate (100-300 microM) but not by 100 microM-2-amino-5-phosphonovalerate (APV). 4. Quisqualate generated smaller, non-desensitizing currents in only 50% of the cells tested (n = 38). Quisqualate responses reversed in polarity near -4 mV and were maximal at an agonist dose of 25 microM, with higher concentrations introducing a rapidly desensitizing component without a detectable increase in amplitude. Currents produced by quisqualate at a concentration of 50 microM were not antagonized by either 750 microM-kynurenate or 100 microM-APV. 5. N-Methyl-D-aspartate (NMDA) produced inward currents at negative holding potentials in 68% of the cells tested (n = 31), but only when magnesium was excluded from the extracellular medium. NMDA currents were non-desensitizing at agonist concentrations of up to 200 microM, with higher concentrations introducing a rapidly desensitizing component. NMDA (200 microM) responses were blocked by APV (100 microM) and kynurenate (300 microM) and reversed near -1 mV. 6. Responses generated by kainate (50-125 microM) were antagonized by quisqualate (30-250 microM). This antagonism occurred even in cells having no measurable response to quisqualate alone, suggesting the possibility that quisqualate may be acting both as an agonist, in the 50% of the cells that have the quisqualate-specific receptor, and as an antagonist, at the kainate-specific site on all cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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