G protein-coupled inwardly rectifying potassium channels (KIR3.1 through KIR3.4) are coupled to numerous neurotransmitter receptors in the brain and are abundantly expressed in the olfactory bulb, hippocampus, neocortex, dentate gyrus, cerebellar cortex and thalamus regions of the brain. Also known as GIRK, KIR3 potassium channels localize to the soma and dendrites as well as axons of neurons. Liberated Gbgamma subunits from G protein heterotrimers bind to and regulate KIR3 channel activity. Gb3- and Gb4-containing Gbgamma dimers bind directly to cytoplasmic domains of KIR3 proteins and increase the K+ current while Gb5-containing Gbgamma dimers inhibit KIR3 K+ current. KIR3 activity is also inhibited by tyrosine phosphorylation. Brain-derived neurotrophic factor activates receptor tyrosine kinase B, which then phosphorylates KIR3 tyrosine residues, effectively inactivating the KIR3 channels.
