Activation of NMDA receptors produces dopamine-mediated changes in fish retinal horizontal cell light responses.
1. The action of N-methyl-D-aspartate (NMDA) on cone horizontal cells was studied in in vitro goldfish retinas superfused with a bicarbonate-based Ringer solution that contained D-serine (0.5 microM), a glycine analogue, but no added Mg2+. Horizontal cell light responses and electrical coupling were assessed by monitoring responses to full-field stimuli and to small, centered (0.4 mm diam) spots of light, respectively. 2. NMDA uncoupled horizontal cells, reduced their light responsiveness, and acted in a dose-dependent manner, with threshold at 10 microM and maximum effect at 100 microM. 3. Application of the NMDA antagonists DL-2-amino-7-phosphonoheptanoic acid-AP-5) or D-2-amino-5-phosphonopentanoic acid-AP-5) (50 microM) blocked the uncoupling action of NMDA (100 microM), as did prior application of SCH23390, a dopamine D1 antagonist, or prior treatment of the retinas with 6-hydroxydopamine, a procedure that destroys dopaminergic neurons. 4. Addition of Mg2+ (1 mM) partially blocked the effects of NMDA at 100 microM and completely blocked the effects of 50 microM NMDA. The effects of NMDA (50 or 100 microM) were also reduced if it was applied without D-serine. 5. Both flickering (5 Hz) and sustained light stimulation uncoupled horizontal cells and reduced their light responsiveness. Application of AP-7 blocked the effects of flickering light stimulation, but did not block the effects of sustained light. 6. These results suggest that activation of NMDA receptors in the fish retina uncouples cone horizontal cells and decreases their light responsiveness by increasing dopamine release. The results further suggest that flickering light, but not sustained light, increases the release of dopamine through activation of NMDA receptors.
Harsanyi
K
K
Department of Ophthalmology, University of Alabama School of Medicine, Birmingham 35294-0021, USA.
Wang
Y
Y
Mangel
S C
SC
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006054:Goldfish / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000528:radiation effects; D010775:Photic Stimulation; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D004298:Dopamine