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.
CITATION STYLE
Hernádez-López, S., Tkatch, T., Perez-Garci, E., Galarraga, E., Bargas, J., Hamm, H., & Surmeier, D. J. (2000). D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLCβ1-IP3-Calcineurin-signaling cascade. Journal of Neuroscience, 20(24), 8987–8995. https://doi.org/10.1523/jneurosci.20-24-08987.2000
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