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Is Protein Kinase C Activity Required for the N ‐Methyl‐ d ‐Aspartate‐evoked Rise in Cytosolic Ca 2+ in Mouse Striatal Neurons?
Author(s) -
Murphy Nuala P.,
Cordier Jocelyne,
Glowinski Jacques,
Prémont Joël
Publication year - 1994
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1994.tb00995.x
Subject(s) - protein kinase c , nmda receptor , staurosporine , activator (genetics) , cytosol , agonist , phorbol , chemistry , protein kinase a , serine , endocrinology , medicine , kinase , biology , receptor , biochemistry , phosphorylation , enzyme
The present study investigates the roles of protein kinase C (PKC) and A (PKA) activities in NMDA‐mediated Ca 2+ entry in primary cultures of mouse striatal neurons. Inhibitors of protein kinases, such as sphingosine, RO 31 – 8220 and staurosporine inhibited the NMDA‐ but also the KCI‐induced rise in cytosolic Ca 2+ . However, the PKA antagonist Rp‐adenosine‐3′,5′monophosphothioate (Rp‐cAMPS) did not alter the NMDA + d ‐serine response, whereas it completely suppressed the KCI response. The NMDA + d ‐serine‐evoked rise in cytosolic Ca 2+ , observed in the absence of external Mg 2+ , was potentiated by the PKC activator phorbol 12‐myristate 13‐acetate (PMA) only when submaximal effective concentrations of this agonist and co‐agonist were used. In addition, the PKC activator did not alter the NMDA + d ‐serine‐evoked response in the presence of varying concentrations of Mg 2+ . Confirming the dependence on PKC activity, desensitization of PKC resulting from long‐term PMA treatment led to an impairment of the NMDA response, leaving the KCI‐induced response intact. We therefore propose that PKC not only potentiates but is also required for the NMDA‐evoked elevation in cytosolic Ca 2+ in mouse striatal neurons.