MODULATION OF THE VOLTAGE-GATED SODIUM CURRENT IN RAT STRIATAL NEURONS BY DARPP-32, AN INHIBITOR OF PROTEIN PHOSPHATASE

Citation
Sn. Schiffmann et al., MODULATION OF THE VOLTAGE-GATED SODIUM CURRENT IN RAT STRIATAL NEURONS BY DARPP-32, AN INHIBITOR OF PROTEIN PHOSPHATASE, European journal of neuroscience, 10(4), 1998, pp. 1312-1320
Citations number
54
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
ISSN journal
0953-816X
Volume
10
Issue
4
Year of publication
1998
Pages
1312 - 1320
Database
ISI
SICI code
0953-816X(1998)10:4<1312:MOTVSC>2.0.ZU;2-D
Abstract
DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of pr otein phosphatase 1, highly enriched in striatonigral neurons. Stimula tion of dopamine D-1 receptors increases phosphorylation of DARPP-32, whereas glutamate acting on N-methy-D-aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for t he function of DARPP-32 in striatal neurons, Using a whole cell patch- clamp technique, we have studied the role of DARPP-32 in the regulatio n of voltage-gated sodium channels in rat striatal neurons maintained in primary culture. Injection of phospho-DARPP-32, but not of the unph osphorylated form, reduced the sodium current amplitude. This effect w as similar to those induced by okadaic acid, with which there was no a dditivity and by tautomycin, Our results indicate that, in striatal ne urons, sodium channels are under dynamic control by phosphorylation/de phosphorylation, and that phospho-DARPP-32 reduces sodium current by s tabilizing a phosphorylated stale of the channel or an associated regu latory protein. We propose that the DARPP-32-mediated modulation of so dium channels, via inhibition of phosphatase 1, contributes to the reg ulation of these channels by D-1 receptors and other neurotransmitters which influence the state of phosphorylation of DARPP-32.