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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mermelstein, P. G. Goldowitz, D. Surmeier, D. J. |
| Description | Author Affiliation: Surmeier DJ ( Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163, USA.); |
| Abstract | The weaver mutation in mice results in a severe ataxia that is attributable to the degeneration of cerebellar granule cells and dopaminergic neurons in the substantia nigra. Recent genetic studies indicate that the GIRK2 gene is altered in weaver. This gene codes for a G-protein-activated, inwardly rectifying K+ channel protein (8). The mutation results in a single amino acid substitution (glycine-->serine) in the pore-forming H5 region of the channel. The functional consequences of this mutation appear to depend upon the co-expression of other GIRK subunits--leading to either a gain or loss of function. Here, we show that G-protein-activated inwardly rectifying K+ currents are significantly reduced in cerebellar granule cells from animals carrying the mutant allele. The reduction is most pronounced in homozygous neurons. These findings suggest that the death of neurons in weaver is attributable to the loss of GIRK2-mediated currents, not to the expression of a nonspecific cation current. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 20 |
| Volume Number | 93 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1996-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cerebellum Physiology Mice, Neurologic Mutants Potassium Channels, Inwardly Rectifying Potassium Channels Potassium Animals Cytology G Protein-Coupled Inwardly-Rectifying Potassium Channels GTP-Binding Proteins Mice Mutation Parkinson Disease Physiopathology Signal Transduction Somatostatin Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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