NR AFIG
AU Herms,J.W.; Korte,S.; Gall,S.; Schneider,I.; Dunker,S.; Kretzschmar,H.A.
TI Altered intracellular calcium homeostasis in cerebellar granule cells of prion protein-deficient mice
QU Journal of Neurochemistry 2000 Oct; 75(4): 1487-92
PT journal article
AB 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 (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 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.
MH Animal; Caffeine/pharmacology; Calcium/*metabolism; Calcium Channel Blockers/pharmacology; Calcium Channels, L-Type/drug effects/metabolism; Cell Differentiation; Cells, Cultured; Cerebellum/cytology/drug effects/*metabolism; Crosses, Genetic; *Homeostasis; Intracellular Fluid/*metabolism; Membrane Potentials/drug effects; Mice; Mice, Knockout; Neurites/metabolism; Patch-Clamp Techniques; Potassium/metabolism/pharmacology; PrPc Proteins/*deficiency/genetics; Support, Non-U.S. Gov't
AD Department of Neuropathology, Georg-August Universität Göttingen, Göttingen, Germany.
SP englisch
PO USA