D2 Dopamine Receptors Reduce N-Type Ca Currents in Rat Neostriatal Cholinergic Interneurons Through a Membrane-Delimited, Protein-Kinase-C-Insensitive Pathway

Yan, Zhen, Wen-Jie Song, and D. James Surmeier. D2 dopamine dopamine (DA) (DeBoer et al. 1993; Di Chiara et al. 1994; receptors reduce N-type Ca currents in rat neostriatal cholinergic Lehman and Langer 1983; Stoof et al. 1982), it is unclear interneurons through a membrane-delimited, protein-kinase-C-insenhow this is accomplished. sitive pathway. J. Neurophysiol. 77: 1003–1015, 1997. Dopamine In other cells, DA exerts its effects through activation of has long been known to regulate the activity of striatal cholinergic G protein-coupled receptors (Sibley 1995). These receptors interneurons and the release of acetylcholine. Yet, the cellular mechacan be grouped into two classes: a D1 class (D1a , D1b) and nisms by which this regulation occurs have not been elucidated. One a D2 class (D2, D3, D4) . In situ hybridization studies have way in which dopamine might act is by modulating voltage-dependent shown that many cholinergic interneurons express D2 mRNA Ca channels. To test this hypothesis, the impact of dopaminergic (Le Moine et al. 1991; Weiner et al. 1991) and a fraction agonists on Ca channels in neostriatal cholinergic interneurons was studied by combined whole cell voltage-clamp recording and singleexpresses D1a receptor mRNA (Le Moine et al. 1991). Imcell reverse transcription–polymerase chain reactions. Cholinergic inmunocytochemical studies have corroborated the localizaterneurons were identified by the presence of choline acetyltransferase tion of D2 receptors (Ariano et al. 1989; Levey et al. 1993) mRNA. Nearly all interneurons tested (90%, n Å 17) coexpressed and recently have suggested that some interneurons may also D2 (short and long isoforms) and D1b (D5) dopamine receptor express D1b receptor protein (Bergson et al. 1995a,b). mRNAs. D1a receptor mRNA was found in only a small subset (20%) One way in which DA receptors might regulate ACh reof the sample and D3 and D4 receptor mRNAs were undetectable. D2 lease is by modulating voltage-dependent Ca channels receptor agonists rapidly and reversibly reduced N-type Ca currents. (Dunlap et al. 1995). In medium spiny neostriatal neurons, D1b/D1a receptor activation had little or no effect on Ca currents. D1-class DA receptors regulate Ca 2/ channels through an The D2 receptor antagonist sulpiride blocked the effect of D2 agonists. adenosine 3*,5 *-cyclic monophosphate (cAMP)-dependent Dialysis with guanosine-5*-O-(2-thiodiphosphate) or brief exposure