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

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 lis 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 ([Ca2+](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 [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 Prnp(O/O) 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.