D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLCβ1-IP3-Calcineurin-signaling cascade

Salvador Hernádez-López, Tatiana Tkatch, Enrique Perez-Garci, Elvira Galarraga, José Bargas, Heidi Hamm, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticle

388 Scopus citations

Abstract

In spite of the recognition that striatal D2 receptors are critical determinants in a variety of psychomotor disorders, the cellular mechanisms by which these receptors shape neuronal activity have remained a mystery. The studies presented here reveal that D2 receptor stimulation in enkephalin-expressing medium spiny neurons suppresses transmembrane Ca2+ currents through L-type Ca2+ channels, resulting in diminished excitabilit. This modulation is mediated by Gβγ activation of phospholipase C, mobilization of intracellular Ca2+ stores, and activation of the calcium-dependent phosphatase calcineurin. In addition to providing a unifying mechanism to explain the apparently divergent effects of D2 receptors in striatal medium spiny neurons, this novel signaling linkage provides a foundation for understanding how this pivotal receptor shapes striatal excitability and gene expression.

Original languageEnglish (US)
Pages (from-to)8987-8995
Number of pages9
JournalJournal of Neuroscience
Volume20
Issue number24
DOIs
StatePublished - Dec 15 2000

Keywords

  • Basal ganglia
  • Calcium
  • Dopamine
  • Electrophysiology
  • Ion channel
  • Medium spiny neuron
  • Neostriatum
  • Neuromodulation
  • Patch clamp
  • Single-cell RT-PCR

ASJC Scopus subject areas

  • Neuroscience(all)

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