Nonselective and G betagamma-insensitive weaver K+ channels.
Homozygous weaver mice are profoundly ataxic because of the loss of granule cell neurons during cerebellar development. This granule cell loss appears to be caused by a genetic defect in the pore region (Gly156-->Ser) of the heterotrimeric guanine nucleotide-binding protein (G protein)-gated inwardly rectifying potassium (K+) channel subunit (GIRK2). A related subunit, GIRK1, associates with GIRK2 to constitute a neuronal G protein-gated inward rectifier K+ channel. The weaver allele of the GIRK2 subunit (wvGIRK2) caused loss of K+ selectivity when expressed either as wvGIRK2 homomultimers or as GIRK1-wvGIRK2 heteromultimers. The mutation also let to loss of sensitivity to G protein betagamma dimers. Expression of wvGIRK2 subunits let to increased cell death, presumably as a result of basal nonselective channel opening.
Navarro
B
B
Department of Pharmacology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Kennedy
M E
ME
Velimirovíc
B
B
Bhat
D
D
Peterson
A S
AS
Clapham
D E
DE
D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics); D016466:CHO Cells; D016923:Cell Death; D002460:Cell Line; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D006224:Cricetinae; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009865:Oocytes / Q000166:cytology; D018408:Patch-Clamp Techniques; D017354:Point Mutation; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D014162:Transfection
D016375:Antisense Elements (Genetics); D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D019204:GTP-Binding Proteins