Death and survival of heterozygous Lurcher Purkinje cells in vitro

Dev Neurobiol. 2009 Jul;69(8):505-17. doi: 10.1002/dneu.20715.


The differentiation and survival of heterozygous Lurcher (+/Lc) Purkinje cells in vitro was examined as a model system for studying how chronic ionic stress affects neuronal differentiation and survival. The Lurcher mutation in the delta2 glutamate receptor (GluRdelta2) converts an orphan receptor into a membrane channel that constitutively passes an inward cation current. In the GluRdelta2(+/Lc) mutant, Purkinje cell dendritic differentiation is disrupted and the cells degenerate following the first week of postnatal development. To determine if the GluRdelta2(+/Lc) Purkinje cell phenotype is recapitulated in vitro, +/+, and +/Lc Purkinje cells from postnatal Day 0 pups were grown in either isolated cell or cerebellar slice cultures. GluRdelta2(+/+) and GluRdelta2(+/Lc) Purkinje cells appeared to develop normally through the first 7 days in vitro (DIV), but by 11 DIV GluRdelta2(+/Lc) Purkinje cells exhibited a significantly higher cation leak current. By 14 DIV, GluRdelta2(+/Lc) Purkinje cell dendrites were stunted and the number of surviving GluRdelta2(+/Lc) Purkinje cells was reduced by 75% compared to controls. However, treatment of +/Lc cerebellar cultures with 1-naphthyl acetyl spermine increased +/Lc Purkinje cell survival to wild type levels. These results support the conclusion that the Lurcher mutation in GluRdelta2 induces cell autonomous defects in differentiation and survival. The establishment of a tissue culture system for studying cell injury and death mechanisms in a relatively simple system like GluRdelta2(+/Lc) Purkinje cells will provide a valuable model for studying how the induction of a chronic inward cation current in a single cell type affects neuronal differentiation and survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cations / metabolism
  • Cell Death / drug effects
  • Cell Death / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cells, Cultured
  • Cerebellar Cortex / growth & development
  • Cerebellar Cortex / metabolism*
  • Cerebellar Cortex / physiopathology
  • Disease Models, Animal
  • Female
  • Ion Channel Gating / genetics
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Male
  • Membrane Potentials / genetics
  • Mice
  • Mice, Neurologic Mutants
  • Mutation / genetics
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Organ Culture Techniques
  • Phenotype
  • Purkinje Cells / metabolism*
  • Purkinje Cells / pathology
  • Receptors, Glutamate / genetics*
  • Receptors, Glutamate / metabolism*
  • Spermine / analogs & derivatives
  • Spermine / pharmacology


  • Cations
  • Ion Channels
  • Receptors, Glutamate
  • glutamate receptor delta 2
  • 1-naphthylacetylspermine
  • Spermine