FUNCTIONAL-EFFECTS OF THE MOUSE WEAVER MUTATION ON G-PROTEIN-GATED INWARDLY RECTIFYING K+ CHANNELS

Citation
Pa. Slesinger et al., FUNCTIONAL-EFFECTS OF THE MOUSE WEAVER MUTATION ON G-PROTEIN-GATED INWARDLY RECTIFYING K+ CHANNELS, Neuron, 16(2), 1996, pp. 321-331
Citations number
60
Categorie Soggetti
Neurosciences
Journal title
NeuronACNP
ISSN journal
08966273
Volume
16
Issue
2
Year of publication
1996
Pages
321 - 331
Database
ISI
SICI code
0896-6273(1996)16:2<321:FOTMWM>2.0.ZU;2-L
Abstract
The weaver mutation corresponds to a substitution of glycine to serine in the H5 region of a G protein-gated inwardly rectifying K+ channel gene (GIRK2). By studying mutant GIRK2 weaver homomultimeric channels and heteromultimeric channels comprised of GIRK2 weaver and GIRK1 in X enopus oocytes, we found that GIRK2 weaver homomultimeric channels los e their selectivity for KC ions, giving rise to inappropriate receptor -activated and basally active Na+ currents, whereas heteromultimers of GIRK2 weaver and GIRK1 appeared to have reduced current. Immunohistoc hemical localization indicates that GIRK2 and GIRK1 proteins are expre ssed in the cerebellar neurons of mice at postnatal day 4, at a time w hen these neurons normally undergo differentiation. Thus, the aberrant behavior of mutant GIRK2 weaver channels could affect the development of weaver mice in at least two distinct ways.