DOPAMINE ALTERS GLUTAMATE-RECEPTOR DESENSITIZATION IN RETINAL HORIZONTAL CELLS OF THE PERCH (PERCA-FLUVIATILIS)

The patch-clamp technique in combination with a fast Liquid filament a pplication system was used to study the effect of dopamine on the glut amate receptor desensitization in horizontal cells of the perch (Perca fluviatilis). Kinetics of ligand-gated ion channels in fish horizonta l cells are modulated by dopamine. This modulation is presumably media ted by a cAMP-dependent protein phosphorylation. Before incubation wit h dopamine, the glutamate receptors of horizontal cells activate and d esensitize with fast time constants. In the whole-cell recording mode, fast application of the agonists L-glutamate, quisqualate, or lpha-am ino-3-hydroxy-5-methyl-4-isoxazolepropionic acid prior to the dopamine incubation gives rise to fast transient currents with peak values of about 200 pA that desensitize within 100 ms. Kainate as agonist produc ed higher steady-state currents but no transient currents. After incub ation of the cells with dopamine for 3 min, the desensitization was si gnificantly reduced and the agonists L-glutamate, quisqualate, or lpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid induced steady-sta te currents with amplitudes that were similar to the previously observ ed transient currents. Kainate-induced currents were only slightly aff ected. Fast desensitizing currents upon fast application of L-glutamat e were also recorded from outside-out patches that were excised from h orizontal cells before incubation with dopamine. The currents from exc ised patches desensitized to a steady-state level of about 0.2 of the peak amplitude with time constants of less than 2 ms. When the outside -out patches were excised from cells after dopamine incubation, steady -state currents were enhanced and no transient currents were observed. The results may indicate that the dopamine dependent modulation of gl utamate-induced currents, which is presumably mediated by a protein ph osphorylation, is due to an alteration of the desensitization of the g lutamate receptors.