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D2Dopamine Receptors in Striatal Medium Spiny Neurons Reduce L-Type Ca2+Currents and Excitability via a Novel PLCβ1–IP3–Calcineurin-Signaling Cascade
Open accessAbstract
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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“This Gαi coupled receptor has been shown to modulate the function of LTCC48,49.”
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Metadata
- 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
- Publisher
- Society for 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
- hybrid
- doi.org
- Licence
- 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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