Altered intracellular calcium homeostasis in cerebellar granule cells of prion protein-deficient mice

J Neurochem. 2000 Oct;75(4):1487-92. doi: 10.1046/j.1471-4159.2000.0751487.x.


Previous studies have indicated that recombinant cellular prion protein (PrP(C)), as well as a synthetic peptide of PrP(C), affects intracellular calcium homeostasis. To analyze whether calcium homeostasis in neurons is also affected by a loss of PrP(C), we performed microfluorometric calcium measurements on cultured cerebellar granule cells derived from prion protein-deficient (Prnp(0/0)) mice. The resting concentration of intracellular free calcium [Ca(2+)](i) was found to be slightly, but significantly, reduced in Prnp(0/0) mouse granule cell neurites. Moreover, we observed a highly significant reduction in the [Ca(2+)](i) increase after high potassium depolarization. Pharmacological studies further revealed that the L-type specific blocker nifedipine, which reduces the depolarization-induced [Ca(2+)](i) increase by 66% in wild-type granule cell somas, has no effect on [Ca(2+)](i) in Prnp(0/0) mouse granule cells. Patch-clamp measurements, however, did not reveal a reduced calcium influx through voltage-gated calcium channels in Prnp(0/0) mice. These data clearly indicate that loss of PrP(C) alters the intracellular calcium homeostasis of cultured cerebellar granule cells. There is no evidence, though, that this change is due to a direct alteration of voltage-gated calcium channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / drug effects
  • Cerebellum / metabolism*
  • Crosses, Genetic
  • Homeostasis*
  • Intracellular Fluid / metabolism*
  • Membrane Potentials / drug effects
  • Mice
  • Mice, Knockout
  • Neurites / metabolism
  • Patch-Clamp Techniques
  • Potassium / metabolism
  • Potassium / pharmacology
  • PrPC Proteins / deficiency*
  • PrPC Proteins / genetics


  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • PrPC Proteins
  • Caffeine
  • Potassium
  • Calcium