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 Gbγ subunits from G protein heterotrimers bind
to and regulate KIR3 channel activity. Gb3- and Gb4-containing Gbγ dimers
bind directly to cytoplasmic domains of KIR3 proteins and increase the K+
current while Gb5-containing Gbγ 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.