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-amino-cyclopentane-1,3-dicarboxylate, an agonist of this type of receptors, on presumed rat dopamine cells intracellularly recorded in vitro. Trans-1-amino-cyclopentane-1,3-dicarboxylate (3-30 muM, t-ACPD) caused a sustained increase of the spontaneous firing rate and a depolarization. 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 current 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 inward 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-phosphonopropionic acid (100 muM), an antagonist of the t-ACPD-induced activation of inositide synthesis. 6-cyano-7-nitroquinoxaline-2,3-dione (10 muM), an alfa-amino-3-hydroxy-5-methyl-isoxazole propionic acid/kainate antagonist, DL-amino-5-phosphonopentanoic acid (30 muM), an N-methyl-D-aspartate antagonist, and scopolamine (10 muM), a muscarinic antagonist, did not significantly affect the actions of t-ACPD. A block of synaptic transmission obtained by applying tetrodotoxin failed to prevent 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 cells decreased in amplitude during membrane hyperpolarization. In approximately 30% of dopamine neurons t-ACPD produced a parallel inward shift of the I-V relation. The cellular response to t-ACPD did not reverse at hyperpolarized potentials in 2.5 mM and 7.5 mM extracellular potassium. It was not modified by the potassium channel blockers tetraethylammonium chloride (10-20 mM), barium (1 mM) or cesium (1-2 mM). It was 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 properties of the t-ACPD-induced responses. Perfusion with a low NaCl solution (choline chloride substitution) reversibly attenuated the t-ACPD-induced inward current. Our data are consistent with the hypothesis that t-ACPD, interacting with metabotropic glutamate receptor, increases the excitability of the rat mesencephalic dopamine neurons. The t-ACPD-induced excitation may be partly attributed to an inward current that is predominately dependent on external sodium ions.