NR AVIS
AU Fuhrmann,M.; Bittner,T.; Mitteregger,G.; Haider,N.; Moosmang,S.; Kretzschmar,H.A.; Herms,J.W.
TI Loss of the cellular prion protein affects the Ca2+ homeostasis in hippocampal CA1 neurons
QU Journal of Neurochemistry 2006 Sep; 98(6): 1876-85
PT journal article
AB Previous neurophysiological studies on prion protein deficient (Prnp(-/-)) mice have revealed a significant reduction of slow afterhyperpolarization currents (sI(AHP)) in hippocampal CA1 pyramidal cells. Here we aim to determine whether loss of PrPc directly affects the potassium channels underlying sI(AHP) or if sI(AHP) is indirectly disturbed by altered intracellular Ca(2+) fluxes. Patch-clamp measurements and confocal Ca(2+) imaging in acute hippocampal slice preparations of Prnp(-/-) mice compared to littermate control mice revealed a reduced Ca(2+) rise in CA1 neurons lacking PrPc following a depolarization protocol known to induce sI(AHP). Moreover, we observed a reduced Ca(2+) influx via l-type voltage gated calcium channels (VGCCs). No differences were observed in the protein expression of the pore forming alpha1 subunit of VGCCs Prnp(-/-) mice. Surprisingly, the beta2 subunit, critically involved in the transport of the alpha1 subunit to the plasma membrane, was found to be up-regulated in knock out hippocampal tissue. On mRNA level however, no differences could be detected for the alpha1C, D and beta2-4 subunits. In conclusion our data support the notion that lack of PrPc does not directly affect the potassium channels underlying sI(AHP), but modulates these channels due to its effect on the intracellular free Ca(2+) concentration via a reduced Ca(2+) influx through l-type VGCCs.
MH Animals; Calcium/*metabolism; Calcium Channels/physiology; Calcium Channels, L-Type/metabolism/physiology; Electrophysiology; Hippocampus/*metabolism; *Homeostasis; In Vitro; Mice; Mice, Inbred Strains; Mice, Knockout; Neurons/*metabolism; Patch-Clamp Techniques; Potassium Channels/metabolism/physiology; Prions; Protein Precursors/*deficiency; Pyramidal Cells/*metabolism/physiology; Research Support, Non-U.S. Gov't
AD Center of Neuropathology and Prion Research, Ludwig Maximilians University, 81377 Munich, Germany.
SP englisch
PO England