WEAVER MUTANT MOUSE CEREBELLAR GRANULE CELLS RESPOND NORMALLY TO CHRONIC DEPOLARIZATION

We studied the effects of chronic K+-induced membrane depolarization a nd treatment with N-methyl-D-aspartate (NMDA) on cerebellar granule ce lls (CGCs) from weaver mutant mice and non-weaver litter-mates. The we aver mutation is a Gly-to-Ser substitution in a conserved region of th e Girk2 G protein-coupled inward rectifying potassium channel [Patil N ., Cox D. R., Bhat D., Flaham M., Myers R. M. and Peterson A. S. (1995 ) Nature Genet. 11, 126-129] which induces early death of CGCs. The bi ochemical differentiation of CGCs was estimated as the rate of 2-deoxy -D-glucose accumulation and the expression of neural cell adhesion mol ecule (NCAM). High (25 mM) K+ ion concentration or treatment with NMDA greatly promoted the biochemical differentiation of both weaver mutan t and non-weaver litter-mate mouse CGCs. In contrast to the marked eff ect on biochemical differentiation in both weaver and non-weaver mice CGSs, chronic high K+ treatment only had limited effect on survival. T he survival of weaver mutant mouse CGCs in medium containing 5 mM K+ i ons was very low, only 20% of the plated cells surviving at 7 days aft er 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 bo th types of culture. The findings indicate that, in culture weaver mut ant mouse, CGCs have a normal response to membrane depolarization and that the normal function of the Girk2 potassium channel is not critica l for the survival of differentiated CGCs. (C) 1997 ISDN.