Weaver mutant mouse cerebellar granule cells respond normally to chronic depolarization.
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.
Bjerregaard
A
A
Laboratory of Neuropsychiatry (Department of Pharmacology, University of Copenhagen), Rigshospitalet, Denmark.
Mogensen
H S
HS
Hack
N
N
Balázs
R
R
Jørgensen
O S
OS
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D003847:Deoxyglucose / Q000378:metabolism; D004594:Electrophysiology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012016:Reference Values; D013997:Time Factors
D019006:Neural Cell Adhesion Molecules; D016202:N-Methylaspartate; D003847:Deoxyglucose; D011188:Potassium