CHARACTERIZATION OF A BARIUM-SENSITIVE OUTWARD CURRENT FOLLOWING GLUTAMATE APPLICATION ON RAT MIDBRAIN DOPAMINERGIC CELLS

Using intracellular electrophysiological recordings in dopaminergic (p rincipal) neurons of the rat mesencephalon maintained in vitro, we stu died a postexcitatory amino acid response (PEAAR). Under current-clamp mode, bath application of glutamate produced a depolarization that wa s followed by a hyperpolarization when the perfusion of the excitatory amino acid was discontinued. Under single-microelectrode voltage-clam p mode, an outward current followed the glutamate-induced inward curre nt. The PEAAR was associated with an increase in membrane conductance and reversed polarity at about -85 mV (2.5 mM extracellular K+). The n ull potential for the PEAAR was independent of the intracellular loadi ng of chloride ions and was shifted towards less negative values (simi lar to 23 mV) by increasing extracellular K+ from 2.5 to 8.5 mM. The P EAAR was present in neurons treated with tetraethylammonium (5-10 mM), apamin (1 mu M) or glibenclamide (1-300 mu M). However, it was strong ly depressed or blocked by extracellular barium (300 mu M to 1 mM), by low-calcium (0.5 mM) plus cadmium (100 mu M) or magnesium (10 mM), an d by low-sodium solutions. An outward response was also generated afte r an inward current induced by the perfusion of the specific agonists for the ionotropic excitatory amino acid receptors NMDA, alpha-amino-3 -hydroxy-5-methyl-4-isoxazole (AMPA) and kainate. The PEAAR was not af fected by tetrodotoxin (1 mu M), saclofen (100-300 mu M), bicuculline (30 mu M), sulpiride (1 mu M) or strychnine (1 mu M). In addition, the inhibition of the ATP-dependent Na+-K+ pump by ouabain and strophanth idin (1-10 mu M) prolonged the glutamate-induced membrane depolarizati on/inward current while the subsequent PEAAR was reduced sr not observ ed. Our data indicate that the PEAAR mainly results from the activatio n of a barium-sensitive potassium current. This response might limit t he excitatory and eventually neurotoxic effects of glutamate.