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

D. James Surmeier*, Jose Bargas, Hugh C. Hemmings, Angus C. Nairn, Paul Greengard

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

456 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)385-397
Number of pages13
JournalNeuron
Volume14
Issue number2
DOIs
StatePublished - Feb 1995

ASJC Scopus subject areas

  • Neuroscience(all)

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