Elevated intracellular calcium levels in cerebellar granule neurons of weaver mice.
Weaver mice carry a mutation in the pore domain of the Girk2 (Kcnj6) gene. The mutation causes GIRK2 containing channels to lose ion selectivity and to become constitutively active. It is not known how this alteration in ion channel activity causes in cerebellar granule cells the defects in neurite extension, cell migration and induction of cell death that are characteristic of weaver mice. One possibility is that the mutation causes an inability to regulate intracellular calcium levels properly. We tested this hypothesis by measuring intracellular calcium levels in granule cells and Purkinje cells in slices from the cerebellum of weaver mice. We report here that weaver mice have increases in resting calcium levels in their granule cells, which may account for the multiple effects of the weaver mutation upon these cells.
Womack
M
M
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.
Thompson
K
K
Fanselow
E
E
Augustine
G J
GJ
Peterson
A
A
D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000378:metabolism*; D009154:Mutation / Q000502:physiology; D009410:Nerve Degeneration / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism*; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying
D005456:Fluorescent Dyes; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D002118:Calcium; D016257:Fura-2