Contrasting calcium dependencies of SAPK and ERK activations by glutamate in cultured striatal neurons

J Neurochem. 1999 Jun;72(6):2248-55. doi: 10.1046/j.1471-4159.1999.0722248.x.


Stress-activated protein kinase (SAPK) and extracellular signal-regulated kinase (ERK), both members of the mitogen-activated protein kinase (MAPK) family, may in some circumstances serve opposing functions with respect to cell survival. However, SAPK and ERK can also be coordinately activated in neurons in response to glutamate stimulation of NMDA receptors. To explore the mechanisms of these MAPK activations, we compared the ionic mechanisms mediating SAPK and ERK activations by glutamate. In primary cultures of striatal neurons, glutamatergic activation of ERK and one of its transcription factor targets, CREB, showed a calcium dependence typical of NMDA receptor-mediated responses. In contrast, extracellular calcium was not required for glutamatergic, NMDA receptor-mediated activation of SAPK and phosphorylation of its substrate, c-Jun. Increasing extracellular calcium enhanced ERK activation but reversed SAPK activation, further distinguishing the calcium dependencies of these two NMDA receptor-mediated effects. Finally, reducing extracellular sodium prevented the glutamatergic activation of SAPK but only partially blocked that of ERK. These contrasting ionic dependencies suggest a mechanism by which NMDA receptor activation may, under distinct conditions, differentially regulate neuronal MAPKs and their divergent functions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Calcium / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cells, Cultured
  • Corpus Striatum / cytology
  • Corpus Striatum / enzymology*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Egtazic Acid / pharmacology
  • Embryo, Mammalian
  • Enzyme Activation
  • Glutamic Acid / pharmacology*
  • Kinetics
  • N-Methylaspartate / pharmacology
  • Neurons / cytology
  • Neurons / enzymology*
  • Phosphorylation
  • Proto-Oncogene Proteins c-jun / metabolism
  • Rats


  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-jun
  • Glutamic Acid
  • Egtazic Acid
  • N-Methylaspartate
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Calcium