Yj. Liao et al., HETEROMULTIMERIZATION OF G-PROTEIN-GATED INWARDLY RECTIFYING K+ CHANNEL PROTEINS GIRK1 AND GIRK2 AND THEIR ALTERED EXPRESSION IN WEAVER BRAIN, The Journal of neuroscience, 16(22), 1996, pp. 7137-7150
The weaver (wv) gene (GIRK2) is a member of the G-protein-gated inward
ly rectifying potassium (GIRK) channel family, known effecters in the
signal transduction pathway of neurotransmitters such as acetylcholine
, dopamine, opioid peptides, and substance P in modulation of neurotra
nsmitter release and neuronal excitability. GIRK2 immunoreactivity is
found in but not limited to brain regions known to be affected in wv m
ice, such as the cerebellar granule cells and dopaminergic neurons in
the substantia nigra pars compacta. It is also observed in the ventral
tegmental area, hippocampus, cerebral cortex, and thalamus. GIRK2 and
GIRK1, a related family member, have overlapping yet distinct distrib
utions in rat and mouse brains. In regions where both channel proteins
are expressed, such as the cerebral cortex, hippocampus, and cerebell
um, they can be co-immunoprecipitated, indicating that they interact t
o form heteromeric channels in vivo. In the brain of the wv mouse, GIR
K2 expression is decreased dramatically. In regions where GIRK1 and GI
RK2 distributions overlap, both GIRK1 and GIRK2 expressions are severe
ly disrupted, probably because of their co-assembly. The expression pa
tterns of these GIRK channel subunits provide a basis for consideratio
n of the machinery for neuronal signaling as well as the differential
effects of the wv mutation in various neurons.