Nonselective and G βγ -Insensitive weaver K + Channels
- 28 June 1996
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 272 (5270) , 1950-1953
- https://doi.org/10.1126/science.272.5270.1950
Abstract
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 led to loss of sensitivity to G protein βγ dimers. Expression of wvGIRK2 subunits led to increased cell death, presumably as a result of basal nonselective channel opening.Keywords
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