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Volume 16, Number 22, Issue of November 15, 1996 pp. 7137-7150
Copyright ©1996 Society for NeuroscienceHeteromultimerization of G-Protein-Gated Inwardly Rectifying K+ Channel Proteins GIRK1 and GIRK2 and Their Altered Expression in weaver Brain
Received Aug. 13, 1996; accepted Aug. 22, 1996.
Y. Joyce Liao, Yuh Nung Jan, and Lily Yeh Jan Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, San Francisco, California 94143-0724
The weaver (wv) gene (GIRK2) is a member of the G-protein-gated inwardly rectifying potassium (GIRK) channel family, known effectors in the signal transduction pathway of neurotransmitters such as acetylcholine, dopamine, opioid peptides, and substance P in modulation of neurotransmitter release and neuronal excitability. GIRK2 immunoreactivity is found in but not limited to brain regions known to be affected in wv mice, 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 distributions in rat and mouse brains. In regions where both channel proteins are expressed, such as the cerebral cortex, hippocampus, and cerebellum, they can be co-immunoprecipitated, indicating that they interact to form heteromeric channels in vivo. In the brain of the wv mouse, GIRK2 expression is decreased dramatically. In regions where GIRK1 and GIRK2 distributions overlap, both GIRK1 and GIRK2 expressions are severely disrupted, probably because of their co-assembly. The expression patterns of these GIRK channel subunits provide a basis for consideration of the machinery for neuronal signaling as well as the differential effects of the wv mutation in various neurons.
Key words: weaver mouse; G-protein; inwardly rectifying potassium channel; dopamine; hippocampus; substantia nigra; cerebellum; heteromultimerization; GIRK
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