Department of Anesthesiology

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Modulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons.

TitleModulation of calcium currents by a D1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons.
Publication TypeJournal Article
Year of Publication1995
AuthorsSurmeier DJ, Bargas J, Hemmings HC, Nairn AC, Greengard P
JournalNeuron
Volume14
Issue2
Pagination385-97
Date Published1995 Feb
ISSN0896-6273
Keywords1-Methyl-3-isobutylxanthine, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester, Animals, Brain, Calcium Channel Blockers, Calcium Channels, Cells, Cultured, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Electrophysiology, Forskolin, Kinetics, Membrane Potentials, Neostriatum, Neurons, Nifedipine, Phosphoprotein Phosphatases, Protein Phosphatase 1, Rats, Rats, Wistar, Receptors, Dopamine D1, Tetraethylammonium, Tetraethylammonium Compounds, Time Factors
Abstract

In rat neostriatal neurons, D1 dopamine receptors regulate the activity of cyclic AMP-dependent protein kinase (PKA) and protein phosphatase 1 (PP1). The influence of these signaling elements on high voltage-activated (HVA) calcium currents was studied using whole-cell voltage-clamp techniques. The application of D1 agonists or cyclic AMP analogs reversibly reduced N- and P-type Ca2+ currents. Inhibition of PKA antagonized this modulation, as did inhibition of PP1, suggesting that the D1 effect was mediated by a PKA enhancement of PP1 activity directed toward Ca2+ channels. In a subset of neurons, D1 receptor-mediated activation of PKA enhanced L-type currents. The differential regulation of HVA currents by the D1 pathway helps to explain the diversity of effects this pathway has on synaptic integration and plasticity in medium spiny neurons.

Alternate JournalNeuron
PubMed ID7531987
Grant ListMH 40899 / MH / NIMH NIH HHS / United States
NS 26473 / NS / NINDS NIH HHS / United States
NS 28889 / NS / NINDS NIH HHS / United States
P01 DA010044 / DA / NIDA NIH HHS / United States