Cited by 444Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchReceptor Mechanisms and Signaling

D2Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca2+Currents and Excitability via a Novel PLCβ1–IP3–Calcineurin-Signaling Cascade

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Hernández-López, Salvador, Tkatch, Tatiana, Perez-Garci, Enrique, Galarraga, Elvira, Bargas, José, Hamm, Heidi, Surmeier, D. James·2000·The Journal of Neuroscience

Abstract

In spite of the recognition that striatal D 2 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 D 2 receptor stimulation in enkephalin-expressing medium spiny neurons suppresses transmembrane Ca 2+currents through L-type Ca 2+channels, resulting in diminished excitability. This modulation is mediated by G βγ activation of phospholipase C, mobilization of intracellular Ca 2+stores, and activation of the calcium-dependent phosphatase calcineurin. In addition to providing a unifying mechanism to explain the apparently divergent effects of D 2 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.

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Crossref · 10.1523/jneurosci.20-24-08987.2000

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  1. Tukey JW (1977) Exploratory data analysis. Menlo Park, CA: Addison- Wesley.

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Authors
Hernández-López, S., Tkatch, T., Perez-Garci, E., Galarraga, E., Bargas, J., Hamm, H., & Surmeier, D. J.
Affiliations
  • Universidad Nacional Autónoma de México (MX)
  • Northwestern University (US)
Venue
The Journal of Neuroscience
Published
2000-12-15
Volume
20
Issue
24
Pages
8987-8995
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W4295332810
Cited by
443
References
60
Citations by year
2026: 9 · 2025: 7 · 2024: 8 · 2023: 15 · 2022: 14 · 2021: 8 · 2020: 15 · 2019: 14 · 2018: 19 · 2017: 13 · 2016: 23 · 2015: 22 · 2014: 20 · 2013: 15 · 2012: 18
FWCI
5.67
Type
journal article
Language
en
Open access
Locations
Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Funders
  • National Institutes of Health (NS 34696)
  • National Institute on Drug Abuse (DA-12958, R01DA012958)
  • National Eye Institute (R01- EY010291)
  • Fogarty International Center (TW 01214)
  • National Institute of Neurological Disorders and Stroke (NS 34696, R01NS034696, R37NS034696)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
dopamine D2 receptor, striatal medium spiny neurons, L-type calcium current, neuronal excitability, PLCB1, IP3 signaling, calcineurin, Gβγ signaling, intracellular calcium stores

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