Weaver mutant mouse cerebellar granule cells respond normally to chronic depolarization
Research output: Contribution to journal › Journal article › Research › peer-review
We studied the effects of chronic K(+)-induced membrane depolarization and treatment with N-methyl-D-aspartate (NMDA) on cerebellar granule cells (CGCs) from weaver mutant mice and non-weaver litter-mates. The weaver mutation is a Gly-to-Ser substitution in a conserved region of the Girk2 G protein-coupled inward rectifying potassium channel [Patil N., Cox D. R., Bhat D., Faham M., Myers R. M. and Peterson A. S. (1995) Nature Genet. 11, 126-129] which induces early death of CGCs. The biochemical differentiation of CGCs was estimated as the rate of 2-deoxy-D-glucose accumulation and the expression of neural cell adhesion molecule (NCAM). High (25 mM) K+ ion concentration or treatment with NMDA greatly promoted the biochemical differentiation of both weaver mutant and non-weaver litter-mate mouse CGCs. In contrast to the marked effect on biochemical differentiation in both weaver and non-weaver mice CGSs, chronic high K+ treatment only had limited effect on survival. The survival of weaver mutant mouse CGCs in medium containing 5 mM K+ ions was very low, only 20% of the plated cells surviving at 7 days after plating, as opposed to the 50% for non-weaver CGCs. Chronic high K+ treatment improved the relative survival of weaver mutant mouse CGCs 1.6 2.2-fold and that of non-weaver CGCs 1.2-1.4-fold; the same number of CGCs (about 20% of the plated cells) were rescued by high K+ in both types of culture. The findings indicate that, in culture weaver mutant mouse, CGCs have a normal response to membrane depolarization and that the normal function of the Girk2 potassium channel is not critical for the survival of differentiated CGCs.
Original language | English |
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Journal | International Journal of Developmental Neuroscience |
Volume | 15 |
Issue number | 2 |
Pages (from-to) | 155-62 |
Number of pages | 7 |
ISSN | 0736-5748 |
Publication status | Published - 1997 |
Bibliographical note
Keywords: Animals; Cell Aging; Cell Differentiation; Cell Survival; Cells, Cultured; Cerebellum; Deoxyglucose; Electrophysiology; Mice; Mice, Neurologic Mutants; N-Methylaspartate; Neural Cell Adhesion Molecules; Potassium; Reference Values; Time Factors
ID: 230158