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 Ca2+ currents through L-type Ca2+ channels, resulting in diminished excitability. This modulation is mediated by G(beta gamma) 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 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.
Última actualización: 14/09/2020