D3 Dopamine Autoreceptors Do Not Activate G-Protein-Gated Inwardly Rectifying Potassium Channel Currents in Substantia Nigra Dopamine Neurons

Substantia nigra (SN) dopamine neurons express D2 and D3 dopamine autoreceptors. A physiological role for the D3 receptor has not been identified, but an activation of G-protein-gated inwardly rectifying potassium (GIRK; also known as Kir3) channels is strongly implicated because D3 receptors activate channels composed of GIRK2 subunits in cell lines. We confirmed that acutely dissociated SN dopamine neurons indeed contain D3 and GIRK2 subunit mRNA using single-cell RT-PCR. We then tested whether D3 receptors activate GIRK currents in SN dopamine neurons by comparing acutely dissociated neurons from D2-/- receptor knock-out and congenic wild-type mice. In nearly all (14 of 15) wild-type SN dopamine neurons, the D2/D3 agonist quinpirole activated GIRK currents that were blocked by cesium. Quinpirole, however, elicited no GIRK currents in any SN dopamine neuron (0 of 13) derived from D2-/- receptor knock-out mice. The absence of quinpirole response was not caused by a lack of GIRK activity, because the GABAB receptor agonist baclofen continued to elicit these currents in the mutant neurons. Thus, it appears that D3 activation of GIRK currents in SN neurons does not occur or is exceedingly rare.