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
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.