DOI:10.22623/IJAPSA.2017.3083.UV7O1 Page 10 GLUCOCORTICOID MEDIATED SPECIFIC REGULATION OF CALCIUM CHANNEL: AN IN SILICO STUDY Sandipan Talukdar 1 , Deep Jyoti Das 2 , Mohan Chandra Kalita 3 and Kandarpa Kr. Saikia 4 1,2 Dept of Bioengineering & Technology, GUIST, Gauhati University 3,4 Dept of Biotechnology, Gauhati University * Corresponding authors: Sandipan Talukdar 1 , Mohan Chandra Kalita 2 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. Keywords: Glucorticoid Receptor, Afterhyperpolarization, VGCC, Glucocorticoid Response Elements, Steroid Hormone I. INTRODUCTION The myriads different and important physiological roles played by steroid hormones have been an active part of research. Among the steroid hormones Glucocorticoid has been reported to be involved in various processes like metabolic, immune response, cognition, development etc [1-5]. Glucocorticoids are produced by the adrenal cortex and secreted from it when the HPA (hipothalamus-pituitary-adrenal) axis is activated in stress response [6]. After secretion, Glucocorticoids can easily diffuse through the cell membrane and thus its cytosolic presence can easily be discerned. The cytosol has an abundance of Glucocorticoid receptor (GR)s, which are bound by the influxed Glucocorticoids. The GR belongs to nuclear receptor family of transcription factor [7]. Once bound by Glucocorticoids, the GR undergoes some conformational changes that can help it migrate to the nucleus and take part in specific gene regulations. Actually the GR in the cytosol resides as a part of a large multi protein complex. This GR associated protein complex includes hsp90, hsp70 and P23 and immunophilins belonging to the FK 506 family [8, 9, 10]. Until bound by Glucocorticoids the GR remains in a conformation that is transcriptionally inactive and unable to translocate to the nucleus. But as soon as the Glucocorticoid binds to it, the GR undergoes a conformational change and gets dissociated from the chaperone proteins [8]. This lead to the ability of the GR to translocate to the nucleus. The GR has a DNA binding domain(DBD), a ligand binding domain(LBD), a hinge region, two activation functions(AF1 and AF2), two nuclear localization signals,NL1 and NL2. The NL1 and NL2 are responsible for its translocation to the nucleus [11]. Once inside the nucleus the GR can bind to the specific genes to be regulated via its DBD. GR binds to specific genes in response to the presence of consensus sequences called the Glucocorticoid