The Journal of Neuroscience, July 2, 2003, 23(13):5693-5697
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BRIEF COMMUNICATION
D3 Dopamine Autoreceptors Do Not Activate G-Protein-Gated Inwardly Rectifying Potassium Channel Currents in Substantia Nigra Dopamine Neurons
Viviana Davila,1
Zhen Yan,4
Liviu C. Craciun,5
Diomedes Logothetis,5 and
David Sulzer1,2,3
Departments of 1Neurology and
2Psychiatry, Columbia University, and
3Department of Neuroscience, New York Psychiatric
Institute, New York, New York 10032,4Department of
Physiology and Biophysics, State University of New York at Buffalo, Buffalo,
New York 14214, and 5Department of Physiology and
Biophysics, Mt. Sinai School of Medicine, New York, New York 10029
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.
Key words: GABA; inwardly rectifying potassium channel; Kir3; single-cell RT-PCR; weaver mouse mutation; ventral tegmental area
Received Feb. 12, 2003;
revised Apr. 16, 2003;
accepted Apr. 16, 2003.
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