Dopaminergic modulation of glutamate-activated channels in the central nervous system

Modulation of glutamate-activated currents by dopamine was studied in identified central neurons, alpha-motoneurons of the chick and horizontal cells of the perch. This modulation is mediated by a cAMP-dependent protein phosphorylation. The activation and desensitization time constants of glutamate currents were determined before and after incubation with dopamine. In the horizontal cells ultrafast glutamate (AMPA or quisqualate) application prior to the the dopamine incubation gives rise to fast transient current responses which desensitize within less than 100 ms. Kainate produced higher steady state currents. After incubation of the cells with dopamine (100 nM) for 30s the desensitization was dramatically reduced, but the amplitudes of the steady state currents were similar to the transient control currents. Kainate activated currents were not affected. In alpha-motoneurons the exposure to dopamine (100 nM) for 1 min was sufficient to increase the peak and steady state amplitudes but not the desensitization time constant of glutamate activated currents. Here enhancement was specific to the kainate component of glutamate activated currents; the decreased variance of currents reflects increased kainate channel activation. Measurements of motoneuronal cAMP concentrations showed an increase following addition of dopamine. mRNA encoding both D1 and D2 dopamine receptor subtypes was detected. We conclude that the dopamine dependent modulation which is mediated by a protein phosphorylation is due to an alteration of the desensitization of AMPA type receptors in horizontal cells and of the activation of kainate type receptors in motoneurons.