Lippincott Williams & Wilkins, Inc., Philadelphia
Altered Intracellular Calcium Homeostasis in Cerebellar Granule Cells of Prion Protein-Deficient Mice
Article first published online: 4 JAN 2002
Journal of Neurochemistry
Volume 75, Issue 4, pages 1487–1492, October 2000
How to Cite
Herms, J. W., Korte, S., Gall, S., Schneider, I., Dunker, S. and Kretzschmar, H. A. (2000), Altered Intracellular Calcium Homeostasis in Cerebellar Granule Cells of Prion Protein-Deficient Mice. Journal of Neurochemistry, 75: 1487–1492. doi: 10.1046/j.1471-4159.2000.0751487.x
Abbreviations used: [Ca2+]i, intracellular free calcium concentration; ω-CgTx, ω-conotoxin; DIV, days in vitro; Prnp0/0, deficient in cellular prion protein; PrPC, cellular prion protein; PrPSc pathological isoform of PrPC; PrP106-126, prion protein peptide corresponding to residue 106-126 of the human prion protein; SOD, superoxide dismutase; VGCC, voltage-gated calcium channel.
- Issue published online: 4 JAN 2002
- Article first published online: 4 JAN 2002
- Prion protein;
- Cerebellar granule cells;
- Whole-cell patch clamp
Abstract: Previous studies have indicated that recombinant cellular prion protein (PrPC), as well as a synthetic peptide of PrPC, affects intracellular calcium homeostasis. To analyze whether calcium homeostasis in neurons is also affected by a loss of PrPC, we performed microfluorometric calcium measurements on cultured cerebellar granule cells derived from prion protein-deficient (Prnp0/0) mice. The resting concentration of intracellular free calcium ([Ca2+]i) was found to be slightly, but significantly, reduced in Prnp0/0 mouse granule cell neurites. Moreover, we observed a highly significant reduction in the [Ca2+]i increase after high potassium depolarization. Pharmacological studies further revealed that the L-type specific blocker nifedipine, which reduces the depolarization-induced [Ca2+]i increase by 66% in wild-type granule cell somas, has no effect on [Ca2+]i in Prnp0/0 mouse granule cells. Patch-clamp measurements, however, did not reveal a reduced calcium influx through voltage-gated calcium channels in Prnp0/0 mice. These data clearly indicate that loss of PrPC 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.