Constitutive calcium entry and cancer: updated views and insights.

Tight control of basal cytosolic Ca concentration is essential for cell survival and to fine-tune Ca-dependent cell functions. A way to control this basal cytosolic Ca concentration is to regulate membrane Ca channels including store-operated Ca channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca channels involved. It is well accepted that, in response to cell stimulation, opening of these Ca channels contributes to Ca entry and the transient increase in cytosolic Ca concentration involved in intracellular signaling. However, in various experimental conditions, Ca entry and/or Ca currents can be recorded at rest, without application of any experimental stimulation. This led to the proposition that some plasma membrane Ca channels are already open/activated in basal condition, contributing therefore to constitutive Ca entry. This article focuses on direct and indirect observations supporting constitutive activity of channels belonging to the Orai and TRP families and on the mechanisms underlying their basal/constitutive activities.