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Loss of the cellular prion protein affects the Ca 2+ homeostasis in hippocampal CA1 neurons
Author(s) -
Fuhrmann Martin,
Bittner Tobias,
Mitteregger Gerda,
Haider Nicole,
Moosmang Sven,
Kretzschmar Hans,
Herms Jochen
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04011.x
Subject(s) - hippocampal formation , afterhyperpolarization , depolarization , prnp , chemistry , biophysics , protein subunit , microbiology and biotechnology , patch clamp , neuroscience , intracellular , membrane potential , potassium channel , calcium , endocrinology , medicine , biology , electrophysiology , biochemistry , gene , allele , organic chemistry
Previous neurophysiological studies on prion protein deficient ( Prnp –/– ) mice have revealed a significant reduction of slow afterhyperpolarization currents (s I AHP ) in hippocampal CA1 pyramidal cells. Here we aim to determine whether loss of PrP C. directly affects the potassium channels underlying s I AHP or if s I 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 PrP C following a depolarization protocol known to induce s I 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 α1 subunit of VGCCs Prnp –/– mice. Surprisingly, the β2 subunit, critically involved in the transport of the α1 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 α1C, D and β2–4 subunits. In conclusion our data support the notion that lack of PrP C. does not directly affect the potassium channels underlying s I 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.