NR ARDV
AU Fuhrmann,M.; Wünsch,G.; Kretzschmar,H.A.; Herms,J.W.
TI Functional role of PrPc in neuronal Ca2+-signaling
QU TSE-Forum, 4. Kongress - Nationale TSE-Forschungsplattform, Düsseldorf 28.10.-29.10.2004, Poster GL-04
PT Konferenz-Poster
AB
PrPc is highly expressed in neurons and plays a critical role in prion diseases, however its physiological function remains unclear. Previous neurophysiologic evaluations of PrP deficient mice showed a significant reduction of slow afterhyperpolarizing currents (sIAHP) in hippocampal CA1 pyramidal cells suggesting a direct role for PrP in the modulation of neuronal excitability.
Here we aim to dissect the contribution of calcium or K+-currents to this phenotype. For that purpose we perform patch clamp and confocal calcium imaging studies in hippocampal slice preparations of PrP deficient mice compared to littermate controls to directly measure the calcium transient and its contribution to the sIAHP.
In Prnp0/0 mice we observed a significant reduction of the maximal amplitude of the calcium transient that directly follows the depolarisation of CA1 neurons. However no alterations were observed in the time course of the calcium decay between Prnp0/0 and littermate controls.
The calcium transient was found to follow a single exponential decay of 3.4 seconds (+/- 0.3 sec; n=29) in Prnp0/0 compared to 3.2 (+/- 0.25 sec; n=31) in wildtype. Moreover simultaneous patch-clamp measurements of the calcium dependent K+-currents did not reveal significant alterations in Prnp0/0 CA1 neurons. The mean amplitude of both the IAHP, 100ms after the end of the stimulus as well as the sIAHP with a maximum at around 700 ms after the end of the stimulus was very similar in Prnp0/0 and wildtype neurons (IAHP: WT=101.9 pA +/- 12.9; Prnp0/0=103.4 pA +/- 13.3; sIAHP: WT=19.3 pA +/- 2.7; Prnp0/0=17.8 pA +/- 2.6).
These results indicate that loss of PrPc affects the calcium influx through the plasma membrane rather than mechanisms that modulate the time course of the calcium decay, like calcium release from intracellular stores, intracellular Ca2+-buffers or Ca2+-extrusion mechanisms.
AD Martin Fuhrmann, Gerda Wünsch, Hans Kretzschmar and Jochen Herms, Center for Neuropathology, LMU, Munich, Germany
SP englisch
PO Deutschland
OR Tagungsband