Regulation of the voltage-gated Ca 2+ channel Ca V α 2 δ-1 subunit expression by the transcription factor Egr-1.

It is well known that the CaV α2 δ auxiliary subunit regulates the density of high voltage-activated Ca2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of CaV α2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of CaV α2 δ. Overexpression and knockdown analysis of Egr-1 showed significant changes in the transcriptional activity of the CaV α2 δ promoter. Egr-1 also regulated the expression of CaV α2 δ at the level of protein. Also, functional studies showed that Egr-1 knockdown significantly decreases Ca2+ currents in dorsal root ganglion (DRG) neurons, while overexpression of the transcription factor increased Ca2+ currents in the F11 cell line, a hybrid of DRG and N18TG2 neuroblastoma cells. Studying the effects of Egr-1 on the transcriptional expression of CaV α2 δ could help to understand the regulatory mechanisms of this protein in both health and disease.