SCIENCE@home

p75 Regulates Purkinje Cell Firing by Modulating SK Channel Activity through Rac1*

J. Tian,Chhavy Tep,Alex Benedick,Nabila Saidi,J. Ryu,Mi Lyang Kim,Shankar Sadasivan,J. Oberdick,Richard J Smeyne,M. Zhu,S. Yoon

Published 2014 in Journal of Biological Chemistry

ABSTRACT

Background: The role of p75 in Purkinje cells of the adult cerebellum has remained obscure. Results: In the absence of p75, RacGTP levels from the cerebellum were reduced, and the mean firing frequency for all phasic firing Purkinje cells was increased. Conclusion: p75 regulates Purkinje cell firing by activating Rac1, thereby targeting SK channel function. Significance: p75 signaling contributes to normal function of Purkinje cell firing. p75 is expressed among Purkinje cells in the adult cerebellum, but its function has remained obscure. Here we report that p75 is involved in maintaining the frequency and regularity of spontaneous firing of Purkinje cells. The overall spontaneous firing activity of Purkinje cells was increased in p75−/− mice during the phasic firing period due to a longer firing period and accompanying reduction in silence period than in the wild type. We attribute these effects to a reduction in small conductance Ca2+-activated potassium (SK) channel activity in Purkinje cells from p75−/− mice compared with the wild type littermates. The mechanism by which p75 regulates SK channel activity appears to involve its ability to activate Rac1. In organotypic cultures of cerebellar slices, brain-derived neurotrophic factor increased RacGTP levels by activating p75 but not TrkB. These results correlate with a reduction in RacGTP levels in synaptosome fractions from the p75−/− cerebellum, but not in that from the cortex of the same animals, compared with wild type littermates. More importantly, we demonstrate that Rac1 modulates SK channel activity and firing patterns of Purkinje cells. Along with the finding that spine density was reduced in p75−/− cerebellum, these data suggest that p75 plays a role in maintaining normalcy of Purkinje cell firing in the cerebellum in part by activating Rac1 in synaptic compartments and modulating SK channels.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-73 of 73 references · Page 1 of 1

CITED BY

Showing 1-17 of 17 citing papers · Page 1 of 1