L-Type Ca2+Channels Are Essential for Glutamate-Mediated CREB Phosphorylation andc-fosGene Expression in Striatal Neurons

• DOI: 10.1523/jneurosci.19-15-06348.1999
• Publication Date: 2018-04-03T10:45:28Z
• Authors: Anjali Rajadhyaksha; Amy Barczak; Wendy Macı́as; Jean-Christophe L...; Susan E. Lewis; Christine Konradi
• Keywords: Neurons; 0301 basic medicine; Calcium Channels, L-Type; Glutamic Acid; Receptors, N-Methyl-D-Aspartate; Corpus Striatum; Rats; Rats, Sprague-Dawley; Calcium Channel Agonists; 03 medical and health sciences; Gene Expression Regulation; Receptors, Glutamate; Receptors, Kainic Acid; Animals; Calcium; Magnesium; Pyrroles; Calcium Channels; Receptors, AMPA; Phosphorylation; Cyclic AMP Response Element-Binding Protein; Proto-Oncogene Proteins c-fos

The second messenger pathways linking receptor activation at the membrane to changes in the nucleus are just beginning to be unraveled in neurons. The work presented here attempts to identify in striatal neurons the pathways that mediate cAMP response element–binding protein (CREB) phosphorylation and gene expression in response to NMDA receptor activation. We investigated the phosphorylation of the transcription factor CREB, the expression of the immediate early genec-fos, and the induction of a transfected reporter gene under the transcriptional control of CREB after stimulation of ionotropic glutamate receptors. We found that neither AMPA/kainate receptors nor NMDA receptors were able to stimulate independently a second messenger pathway that led to CREB phosphorylation orc-fosgene expression. Instead, we saw a consecutive pathway from AMPA/kainate receptors to NMDA receptors and from NMDA receptors to L-type Ca2+channels. AMPA/kainate receptors were involved in relieving the Mg2+block of NMDA receptors, and NMDA receptors triggered the opening of L-type Ca2+channels. The second messenger pathway that activates CREB phosphorylation andc-fosgene expression is likely activated by Ca2+entry through L-type Ca2+channels. We conclude that in primary striatal neurons glutamate-mediated signal transduction is dependent on functional L-type Ca2+channels.