Glucocorticoid mediated Specific Regulation of Calcium Channel: An in silico study

Abstract

The role played by steroid hormones in managing stress and homeostasis is extremely important from physiological perspective. Glucorticoid, one of the main steroid hormones bears an important position in this respect. Glucocorticoid confers its activity by precise and specific regulation of certain genes. It adopts a mechanism where it binds to its receptor in the cytosol and translocates to the nucleus and hereby activates or represses particular genes. The voltage gated calcium channels (VGCC) play important roles in neuronal firing. Between the L type and N type VGCC, Glucocorticoid specifically enhance the L type. This is important in regulating the neuronal excitability as enhanced L type current leads the cell to more hyperpolarized state and thus reducing excitability. Here we have studied the factors governing the glucocorticoid mediated control of VGCC. We found that the locus of the glucocorticoid receptor response elements (GRE) and negative GRE (nGRE), nucleosome positioning, the binding affinity of Glucocorticoid receptor (GR) to GRE and nGRE are the factors that lead to specific enhancement of L type over N type VGCC mediated by GR.