Though most neurons express GIRK1, 2 and 3, dopamine (DA) neurons of the SN and VTA do not express GIRK1-containing GIRKs. In SN dopamine neurons, for example, GIRK channels are comprised of GIRK2a/2c subunits41. In the VTA dopamine neurons, some GIRK channels are heterotetramers of GIRK2c/GIRK343. It is not well understood why DA neurons express a unique combination of GIRK subunits but GIRK2/3 channels are less sensitive to Gβγ subunits and exhibit a higher EC50 for coupling to GABAB receptors than GIRK1-containing channels20,43. This difference in sensitivity has been linked to important changes in the output of the drug reward pathway (see below).
