Properties and Functions of Store-Operated Calcium Entry in the Developing Nervous System

Abstract

Store-operated calcium channels (SOCs) open in response to depletion of calcium stores in the endoplasmic reticulum. These channels are expressed in a variety of tissues including the immune system, vasculature and hepatocytes. The most widely studied and characterized SOC is the Calcium Release-Activated Calcium (CRAC) channel in the immune system. Recent findings indicate that CRAC channels are activated by local interactions between the ER Ca2+ sensor, STIM1 and the CRAC channel subunit, ORAI1. Calcium influx through these channels has been shown to play an important role in transcription of inflammatory mediators such as interleukins and cytokines, mediated by the transcription factor NFAT1.The current study aims at characterizing these channels in the developing nervous system. Calcium imaging experiments demonstrate the presence of store-operated calcium entry (SOCE) with properties similar to that mediated by the CRAC channel. Calcium influx following store-depletion is blocked by La3+, a potent CRAC channel blocker. In addition, 2-APB (0.01–0.02 mM) causes a transient elevation in intracellular calcium followed by a decrease, consistent with that observed in immune cells. Functional studies done using NFAT1 tagged to GFP show translocation of this transcription factor to the nucleus upon calcium entry following store-depletion. Further, we find an increase in the levels of endogenous NFAT-dependent gene expression using Luciferase reporter assays. Altogether, these results provide evidence for the existence of store-operated calcium entry in the developing nervous system and point towards a regulatory role for this pathway in gene-transcription.