Linked Life Data

9570785

Source:http://linkedlifedata.com/resource/pubmed/id/9570785

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-6-1
pubmed:abstractText
Considerable interest has recently focused on the weaver mutation, which causes inward rectifier channel alterations leading to profound impairment of neuronal differentiation and to severe motor dysfunction in mice (Hess, 1996). The principal targets of mutation are cerebellar granule cells, most of which fail to differentiate and degenerate in a premigratory position (Rakic and Sidman, 1973a,b). Two hypotheses have been put forward to explain the pathogenetic role of mutant inward rectifier channels: namely that inward rectifier channel activity is either lacking (Surmeier et al., 1996) or altered (Kofuji et al., 1996; Silverman et al., 1996; Slesinger et al., 1996). We have examined this question by recording inward rectifier currents from cerebellar granule cells in situ at different developmental stages in wild-type and weaver mutant mice. In wild-type mice, the inward rectifier current changed from a G-protein-dependent activation to a constitutive activation as granule cells developed from premigratory to postmigratory stages. In weaver mutant mice, G-protein-dependent inward rectifier currents were absent in premigratory granule cells. A population of putative granule cells in the postmigratory position expressed a constitutive inward rectifier current with properties compatible with mutated GIRK2 channels expressed in heterologous systems. Because granule cells degenerate at the premigratory stage (Smeyne and Goldowitz, 1989), the loss of inward rectifier current and its regulation of membrane potential are likely to play a key role in the pathogenesis of weaver neuronal degeneration.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3537-47
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9570785-Anesthetics, Local, pubmed-meshheading:9570785-Animals, pubmed-meshheading:9570785-Cell Movement, pubmed-meshheading:9570785-Cerebellum, pubmed-meshheading:9570785-Female, pubmed-meshheading:9570785-G Protein-Coupled Inwardly-Rectifying Potassium Channels, pubmed-meshheading:9570785-GTP-Binding Proteins, pubmed-meshheading:9570785-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:9570785-Lidocaine, pubmed-meshheading:9570785-Male, pubmed-meshheading:9570785-Membrane Potentials, pubmed-meshheading:9570785-Mice, pubmed-meshheading:9570785-Mice, Neurologic Mutants, pubmed-meshheading:9570785-Nerve Degeneration, pubmed-meshheading:9570785-Patch-Clamp Techniques, pubmed-meshheading:9570785-Potassium Channels, pubmed-meshheading:9570785-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:9570785-Receptors, Muscarinic
pubmed:year
1998
pubmed:articleTitle
The weaver mutation causes a loss of inward rectifier current regulation in premigratory granule cells of the mouse cerebellum.
pubmed:affiliation
Istituto di Fisiologia Generale, I-27100, Pavia, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't