Dopaminergic Modulation of NMDA-Induced Whole Cell Currents in Neostriatal Neurons in Slices: Contribution of Calcium Conductances

Carlos Cepeda 1 , Christopher S. Colwell 1 , Jason N. Itri 1 , Scott H. Chandler 1 , 2 , and Michael S. Levine 1 Mental Retardation Research Center and 2 Department of Physiological Science, University of California, Los Angeles, California 90024-1759 Cepeda, Carlos, Christopher S. Colwell, Jason N. Itri, Scott H. Chandler, and Michael S. Levine. Dopaminergic modulation of NMDA-induced whole cell currents in neostriatal neurons in slices: contribution of calcium conductances. J. Neurophysiol. 79: 82-94, 1998. The present experiments were designed to examine dopamine (DA) modulation of whole cell currents mediated by activation of N -methyl- D -aspartate (NMDA) receptors in visualized neostriatal neurons in slices. First, we assessed the ability of DA, D 1 and D 2 receptor agonists to modulate membrane currents induced by activation of NMDA receptors. The results of these experiments demonstrated that DA potentiated NMDA-induced currents in medium-sized neostriatal neurons. Potentiation of NMDA currents occurred at three different holding potentials, although it was more pronounced at 30 mV. It was mediated by D 1 receptors, because it was mimicked by D 1 agonists and blocked by exposure to a D 1 antagonist. Activation of D 2 receptors produced inconsistent effects on NMDA-induced membrane currents. Either decreases, increases, or no effects on NMDA currents occurred. Second, we examined the contributions of intrinsic, voltage-dependent conductances to DA potentiation of NMDA currents. Blockade of K + conductances did not prevent DA enhancement of NMDA currents. However, voltage-activated Ca 2+ conductances provided a major contribution to DA modulation. The dihydropyridine L-type Ca 2+ channel blockers, nifedipine, and methoxyverapamil (D 600), markedly reduced but did not totally eliminate the ability of DA to modulate NMDA currents. The D 1 receptor agonist SKF 38393 also enhanced Ba 2+ currents in neostriatal neurons. Together, these findings provide evidence for a complex interplay between DA, NMDA receptor activation and dihydropyridine-sensitive Ca 2+ conductances in controlling responsiveness of neostriatal medium-sized neurons.