Is protein kinase C activity required for the N-methyl-D-aspartate-evoked rise in cytosolic Ca2+ in mouse striatal neurons?
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 sphingosine, RO 31-8220 and staurosporine inhibited the NMDA- but also the KCl-induced rise in cytosolic Ca2+. However, the PKA antagonist Rp-adenosine-3',5'monophosphothioate (Rp-cAMPS) did not alter the NMDA+D-serine response, whereas it completely suppressed the KCl response. The NMDA+D-serine-evoked rise in cytosolic Ca2+, observed in the absence of external Mg2+, 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 Mg2+. 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 KCl-induced response intact. We therefore propose that PKC not only potentiates but is also required for the NMDA-evoked elevation in cytosolic Ca2+ in mouse striatal neurons.
Murphy
N P
NP
Laboratoire de Neuropharmacologie, INSERM U114, Collège de France, Paris.
Cordier
J
J
Glowinski
J
J
Prémont
J
J
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000494:pharmacology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D000470:Alkaloids; D007211:Indoles; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D016202:N-Methylaspartate; D011189:Potassium Chloride; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C064758:Ro 31-8220