Effects of Dopamine on Glutamate Responses in Horizontal and Bipolar Cells Isolated From Zebrafish Retina

Abstract

Abstract: : Purpose: The purpose of this study is to determine the effects of dopamine on isolated zebrafish retina cell responses to glutamate. Methods: Glutamate responses of papain dissociated horizontal and bipolar cells were studied with the voltage probe oxonol, DiBaC₄(5). Such responses were then recorded in the presence of selective dopamine agonists and antagonists. Results: In general glutamate voltage responses were found to increase in the presence of dopamine, the D₁ agonist SKF 38393, or the D₂ agonist quinpirole. Effects of dopamine antagonists were both consistent and prominent, but presented a more complex picture. In the presence of dopamine, the D₂ antagonist sulpiride and the D₁ antagonist SCH 23390 further increased glutamate voltage responses. In the presence of glutamate and SKF 38393, SCH 23390 potentiated the glutamate response, however, the glutamate–quinpirole potentiation was inhibited by sulpiride. Application of tetraethylammonium potentiated the glutamate response with dopamine, D₁ or D₂ agonists. Conclusions: These results suggest two opposing dopamine receptor mechanisms, each activated by D₁ or D₂ receptors. In the excitatory mechanism, dopamine or its agonists potentiate the glutamate response. Only the D₂ antagonist acting at the D₂ receptor can be seen to suppress this effect. In the inhibitory mechanism, the D₁ receptor has a D₂ antagonist binding site. One possibility for an inhibitory second site of action is stimulation of outwardly rectifying potassium currents by dopamine (Fan and Yazulla, 1999). These currents tend to reduce the voltage amplitude of glutamate responses. Blockade of potassium channel enhancement by selective dopamine antagonists might then further augment glutamate voltage responses.

Keywords: excitatory neurotransmitters • retina: distal (photoreceptors, horizontal cells, bipolar cells) • dopamine