Responses mediated by excitatory amino acid receptors in solitary retinal ganglion cells from rat.

Abstract

SUMMARY1. 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 ,UM 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 ,uM) 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 /tM-kainate were reversibly antagonized by kynurenate (100-300 ,PM) but not by 100 ,tm-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 PM, with higher concentrations introducing a rapidly desensitizing component without a detectable increase in amplitude. Currents produced by quisqualate at a concentration of 50 ,UM were not antagonized by either 750 jtM-kynurenate or 100 1sM-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 PM, with higher concentrations introducing a rapidly desensitizing component. NMDA (200 PM) responses were blocked by APV (100 uM) and kynurenate (300 PM) and reversed near -1 mV.6. Responses generated by kainate (50-125 PM) were antagonized by quisqualate (30-250 uM

Localization and developmental expression of the NMDA receptor subunit NR2A in the mammalian retina

“…In recordings from dissociated ganglion cells from rat retina, Aizenman et al (1988) found that NMDA-evoked inward currents were practically abolished by the presence of 1 mM Mg2+ in the extracellular fluid. This is consistent with our results because coexpression of NR1 and NR2A results in receptors with high sensitivity to Mg2+ (Kutsuwada et al, 1992;Meguro et al, 1992;Monyer et d .…”

“…, 1992). Aizenman et al (1988) detected NMDA-evoked currents in only 68% of dissociated cells. Our finding that the immunoreactivity is localized on ganglion cell dendrites in the IPL suggests that the absence of NMDA responses in some dissociated cells could be an artefact due to loss of dendrites during the dissociation procedure.…”

“…Due to their unique biophysical and pharmacological properties, such as Mg2 + -dependent voltage block (Nowak et al, 19841, Ca2+ permeability (MacDermott et al, 19861, potentiation by glycine (Johnson and Ascher, 1987), and slow kinetics (Collingridge et al, 1988;Forsythe and Westbrook, 19881, particular attention has been devoted to the NMDA receptors, which seem to be involved in neuronal signalling in the IPL (Slaughter and Miller, 1983b;Aizenman et al, 1988;Coleman and Miller, 1988;Massey andMiller, 1988, 1990;Boos et al, 1990;Mittman et al, 1990;Linn and Massey, 1991;Dixon and Copenhagen, 1992;Gottesman and Miller, 1992).…”

A Review of Glutamate Receptors I: Current Understanding of Their Biology

“…Physiological studies using isolated cells indicate that only µM levels of Glu are required to activate GluR [106][107][108] . Thus, the amount of Glu released into the synaptic cleft is several orders of magnitude higher than the concentration required for activating most postsynaptic receptors.…”

Pharmacodynamics of citicoline relevant to the treatment of glaucoma

“…RGC display a variety of glutamate receptors (Aizenman et al, 1988), and they actually were the first neurons in which glutamate-induced cell death was demonstrated (Lucas and Newhouse, 1957). Several lines of evidence are suggestive of the involvement of glutamate excitotoxicity in the pathogenesis of glaucoma (Vorwerk et al, 1999).…”