Dopaminergic Modulation of NMDA-Induced Whole-Cell Currents in Neostriatal
Neurons in Slices: Contribution of Calcium Conductances.
Carlos Cepeda, Christopher S. Colwell, Jason N. Itri, Scott H. Chandler and
Michael S. Levin
Mental Retardation Research Center and Department of Physiological Science,
University of California, Los Angeles, Los Angeles, CA 90024-1759.
APStracts 4:277N, 1997.
ABSTRACT
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, since 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 (D-600), 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.
Received 5 June 1997; accepted in final form 23 September 1997.
APS Manuscript Number J463-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997