Np. Murphy et al., IS PROTEIN-KINASE-C ACTIVITY REQUIRED FOR THE N-METHYL-D-ASPARTATE-EVOKED RISE IN CYTOSOLIC CA2+ IN MOUSE STRIATAL NEURONS, European journal of neuroscience, 6(5), 1994, pp. 854-860
The present study investigates the roles of protein kinase C (PKC) and
A (PKA) activities in NMDA-mediated Ca2+ entry in primary cultures of
mouse striatal neurons. Inhibitors of protein kinases, such as sphing
osine, RO 31 - 8220 and staurosporine inhibited the NMDA- but also the
KCl-induced rise in cytosolic Ca2+. However, the PKA antagonist Rp-ad
enosine-3',5'monophosphothioate (Rp-cAMPS) did not alter the NMDA + D-
serine response, whereas it completely suppressed the KCl response. Th
e NMDA + D-serine-evoked rise in cytosolic Ca2+, observed in the absen
ce of external Mg2+, was potentiated by the PKC activator phorbol 12-m
yristate 13-acetate (PMA) only when submaximal effective concentration
s of this agonist and co-agonist were used. In addition, the PKC activ
ator did not alter the NMDA + D-serine-evoked response in the presence
of varying concentrations of Mg2+. Confirming the dependence on PKC a
ctivity, desensitization of PKC resulting from longterm PMA treatment
led to an impairment of the NMDA response, leaving the KCl-induced res
ponse intact. We therefore propose that PKC not only potentiates but i
s also required for the NMDA-evoked elevation in cytosolic Ca2+ in mou
se striatal neurons.