Excitatory amino acids in synaptic excitation of rat striatal neurones in vitro.

1. Intracellular recordings were made from rat striatal neurones in vitro. The cells had resting membrane potentials greater than -60 mV and action potentials greater than 70 mV with spike overshoot of 10-30 mV. 2. In the presence of bicuculline intrastriatal stimulation evoked an excitatory postsynaptic potential (EPSP). The relationship between EPSP amplitude and membrane potential was not linear. The EPSP decreased in amplitude and duration for values of membrane potential more negative than -80 mV and increased in amplitude and duration for values of membrane potential more positive than -50 mV. 3. The mean reversal potential for the EPSP recorded with electrodes filled with potassium methyl-sulphate was -9.2 +/- 1.7 mV (mean +/- S.E.M.) in presence of bicuculline (30 microM). A similar reversal potential was obtained with CsCl-filled electrodes. 4. The endogenous broad-spectrum excitatory amino acid antagonist, kynurenic acid (100-500 microM), reduced the EPSP in a dose-dependent way, maximally by 80% at 500 microM, but a residual depolarization remained even at high antagonist concentrations. This effect was associated sometimes with a membrane depolarization and an increase in input resistance. 5. In normal artificial cerebro-spinal fluid solution and at resting membrane potential the specific N-methyl-D-aspartate (NMDA) antagonist, (D,L)-2-amino-7-phosphonoheptanoic acid (([D,L)-AP7), did not affect the EPSP amplitude. However, this antagonist partially reduced the EPSP amplitude when the membrane was depolarized beyond -50 mV by intracellular current injection. 6. The nicotinic cholinergic antagonist mecamylamine (10 microM) caused a partial (24 +/- 3%) reduction of EPSP amplitude at resting potential in normal medium. However, in the cells where a reduction of EPSP amplitude was observed it was always accompanied by membrane depolarization (7.1 +/- 2.1 mV). (+)-Tubocurarine and hexamethonium were without effect at 10 microM. 7. When Mg2+ was removed from the bathing solution, the EPSP increased in amplitude (89 +/- 9.5%) and duration. In Mg2+-free medium at resting membrane potential (D,L)-AP7 (30 microM) partially reduced EPSP amplitudes (59 +/- 2.5%). 8. It is proposed that a major component of the EPSP evoked by intrastriatal stimulation is mediated by excitatory amino acids. At resting membrane potential and in normal medium only non-NMDA receptors seem to contribute to the synaptic depolarization, but at depolarized potentials and in Mg2+-free medium an NMDA receptor-mediated component of the EPSP can be demonstrated.