ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS INDUCES AN INWARD CURRENT IN RAT DOPAMINE MESENCEPHALIC NEURONS

To investigate the electrophysiological effects of the stimulation of the metabotropic excitatory amino acid receptors, we applied trans-1-a mino-cyclopentane-1,3-dicarboxylate, an agonist of this type of recept ors, on presumed rat dopamine cells intracellularly recorded in vitro. Trans-1-amino-cyclopentane-1,3-dicarboxylate (3-30 muM, t-ACPD) cause d a sustained increase of the spontaneous firing rate and a depolariza tion. When the membrane potential was held at about the resting level (-50, -60 mV), by the single-electrode voltage-clamp technique, t-ACPD induced an inward current. In 57% of the tested cells the inward curr ent was associated with a decrease of the apparent input conductance. In the remaining cells no obvious changes in membrane conductance were observed. The active form of t-ACPD, (1S,3R)-1-amino-cyclopentane-1,3 -dicarboxylate [3-50 muM, (1S,3R)-ACPD] also produced a reversible inw ard current on the dopaminergic cells and this was antagonized by (S)- 4-carboxy-3-hydroxyphenylglycine (300 muM), a selective antagonist of the (1S,3R)-ACPD-induced depolarization on central neurons. The (1S,3R )-ACPD-induced inward current was not antagonized by L-2-amino-3-phosp honopropionic acid (100 muM), an antagonist of the t-ACPD-induced acti vation of inositide synthesis. 6-cyano-7-nitroquinoxaline-2,3-dione (1 0 muM), an alfa-amino-3-hydroxy-5-methyl-isoxazole propionic acid/kain ate antagonist, DL-amino-5-phosphonopentanoic acid (30 muM), an N-meth yl-D-aspartate antagonist, and scopolamine (10 muM), a muscarinic anta gonist, did not significantly affect the actions of t-ACPD. A block of synaptic transmission obtained by applying tetrodotoxin failed to pre vent the action of t-ACPD. The t-ACPD-induced current was inward from approximately -40 to -115 mV and in approximately 70% of the tested ce lls decreased in amplitude during membrane hyperpolarization. In appro ximately 30% of dopamine neurons t-ACPD produced a parallel inward shi ft of the I-V relation. The cellular response to t-ACPD did not revers e at hyperpolarized potentials in 2.5 mM and 7.5 mM extracellular pota ssium. It was not modified by the potassium channel blockers tetraethy lammonium chloride (10-20 mM), barium (1 mM) or cesium (1-2 mM). It wa s present in low calcium (0.5 mM) plus magnesium (10-20 mM) or cobalt (1-2 mM). Shifting the Cl- equilibrium potential did not affect the pr operties of the t-ACPD-induced responses. Perfusion with a low NaCl so lution (choline chloride substitution) reversibly attenuated the t-ACP D-induced inward current. Our data are consistent with the hypothesis that t-ACPD, interacting with metabotropic glutamate receptor, increas es the excitability of the rat mesencephalic dopamine neurons. The t-A CPD-induced excitation may be partly attributed to an inward current t hat is predominately dependent on external sodium ions.