Potassium chloride depolarization mediates CREB phosphorylation in striatal neurons in an NMDA receptor-dependent manner

Potassium chloride (KCl)-depolarization has been used to study the properti es of L-type Ca2+ channel-mediated signal transduction in hippocampal neuro ns. Calcium influx through L-type Ca2+ channels stimulates a second messeng er pathway that transactivates genes under the regulatory control of the Ca 2+- and cyclic AMP-responsive element (CRE). Here, we show that in striatal neurons, but not in hippocampal neurons, CRE binding protein (CREB) phosph orylation and CRE-mediated gene expression after KCl-depolarization depends on functional NMDA receptors. This difference in NMDA receptor dependence is not due to different properties of L-type Ca2+ channels in either neuron al type, but rather to different neuron-intrinsic properties. Despite this variation, the second messenger pathway activated by KCI requires Ca2+/calm odulin (CaM) kinase for CREB phosphorylation in both neuronal types. We con clude that depolarization by KCl works differently in striatal and hippocam pal neurons. (C) 2001 Elsevier Science BN. All rights reserved.