The Journal of Neurophysiology Vol. 79 No. 1 January 1998, pp. 82-94
Copyright ©1998 The American Physiological Society

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

Carlos Cepeda¹, Christopher S. Colwell¹, Jason N. Itri¹, 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, D₁ and D₂ 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 D₁ receptors, because it was mimicked by D₁ agonists and blocked by exposure to a D₁ antagonist. Activation of D₂ 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 Ca²⁺ conductances provided a major contribution to DA modulation. The dihydropyridine L-type Ca²⁺ channel blockers, nifedipine, and methoxyverapamil (D600), markedly reduced but did not totally eliminate the ability of DA to modulate NMDA currents. The D₁ receptor agonist SKF 38393 also enhanced Ba²⁺ currents in neostriatal neurons. Together, these findings provide evidence for a complex interplay between DA, NMDA receptor activation and dihydropyridine-sensitive Ca²⁺ conductances in controlling responsiveness of neostriatal medium-sized neurons.

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