Monitoring of intra-ER free Ca2+

Abstract

The importance of calcium signaling in cell health and disease is the major driving force in current research of intracellular calcium homeostasis. Ca2+ release from the endoplasmic reticulum (ER) and other calcium stores seems to be the crucial factor in the activation of many cellular functions. Significant changes in ER Ca2+ content and dynamics have been implicated in the activation of the ER stress response, abnormal autophagy, and cell death which leads to a variety of pathological conditions. For example, in acute pancreatitis, an inflammatory disease of the exocrine pancreas caused primarily by bile stones or alcohol, excessive intracellular calcium overload due to Ca2+ release from internal stores followed by store operated Ca2+ entry (SOCE) leads to the premature activation of digestive proenzymes within pancreatic acinar cells. Recent data show that SOCE channel blockers are capable of substantially reducing the intracellular Ca2+ overload and subsequent cell necrosis without major alteration of ER Ca2+ content. We also demonstrate here that indirect ER measurements can be misleading and only direct intra-ER Ca2+ monitoring offers reliable conclusions. In this respect, it is essential to summarize the methods available and provide examples of direct measurements of free Ca2+ concentration [Ca2+] in the ER lumen in pancreatic acinar cells. This article is aimed at highlighting the major techniques for monitoring ER Ca2+ with reference to their advantages, limitations, and views for future improvements. WIREs Membr Transp Signal 2014,3:63-71. doi: 10.1002/wmts.106 For further resources related to this article, please visit the WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 3 3 May/June 2014 10.1002/wmts.106 Focus Article Focus Article © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.