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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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1-Methyl-3-isobutylxanthine / pharmacology
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
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Animals
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Brain / drug effects
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Brain / physiology*
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Calcium Channel Blockers / pharmacology*
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Calcium Channels / physiology*
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Cells, Cultured
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Colforsin / analogs & derivatives
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Colforsin / pharmacology
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Electrophysiology / methods
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Kinetics
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Membrane Potentials / drug effects
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Neostriatum / enzymology
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Neostriatum / physiology*
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Neurons / drug effects
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Neurons / enzymology
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Neurons / physiology*
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Nifedipine / pharmacology
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Phosphoprotein Phosphatases / metabolism*
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Protein Phosphatase 1
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Rats
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Rats, Wistar
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Receptors, Dopamine D1 / agonists
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Receptors, Dopamine D1 / physiology*
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Tetraethylammonium
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Tetraethylammonium Compounds / pharmacology
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Time Factors
Substances
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Calcium Channel Blockers
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Calcium Channels
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Receptors, Dopamine D1
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Tetraethylammonium Compounds
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Colforsin
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Tetraethylammonium
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
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3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Phosphoprotein Phosphatases
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Protein Phosphatase 1
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Nifedipine
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1-Methyl-3-isobutylxanthine