Ca²⁺ tunnelling through the ER lumen as a mechanism for delivering Ca²⁺ entering via store‐operated Ca²⁺ channels to specific target sites

Abstract

Ca2+ signalling is perhaps the most universal and versatile mechanism regulating a wide range of cellular processes. Because of the many different calcium‐binding proteins distributed throughout cells, signalling precision requires localized rises in the cytosolic Ca2+ concentration. In electrically non‐excitable cells, for example epithelial cells, this is achieved by primary release of Ca2+ from the endoplasmic reticulum via Ca2+ release channels placed close to the physiological target. Because any rise in the cytosolic Ca2+ concentration activates Ca2+ extrusion, and in order for cells not to run out of Ca2+, there is a need for compensatory Ca2+ uptake from the extracellular fluid. This Ca2+ uptake occurs through a process known as store‐operated Ca2+ entry. Ideally Ca2+ entering the cell should not diffuse to the target site through the cytosol, as this would potentially activate undesirable processes. Ca2+ tunnelling through the lumen of the endoplasmic reticulum is a mechanism for delivering Ca2+ entering via store‐operated Ca2+ channels to specific target sites, and this process has been described in considerable detail in pancreatic acinar cells and oocytes. Here we review the most important evidence and present a generalized concept.

Type 3 Inositol 1,4,5-Trisphosphate Receptor is a Crucial Regulator of Calcium Dynamics Mediated by Endoplasmic Reticulum in HEK Cells

“…Together, these results showed that the expression of IP 3 R3 also could regulate SOCE in HEK cells. It is known that SOCE-mediating CRAC channels, SERCA and IP 3 Rs are functionally coupled under physiological conditions [24][25][26]43]. Our results thus added a new aspect of couplings among Ca 2+ handling machineries.…”

Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology

“…Ca 2+ signalling studies on isolated pancreatic acinar cells (PACs) or small acinar cell clusters have led to a detailed understanding of the mechanisms underlying the primary intracellular Ca 2+ release elicited by physiological and pathological agents as well as the subsequent opening of store-operated Ca 2+ channels in the plasma membrane that accounts for the secondary Ca 2+ entry from the extracellular solution Petersen et al 2017). Physiological, short-lasting and repetitive local Ca 2+ signals control acinar fluid and enzyme secretion (Petersen, 1992;, whereas sustained global elevations of the cytosolic Ca 2+ concentration ([Ca 2+ ] i ), elicited by pathological agents, play a key role in the development of the acinar cell damage and death leading to acute pancreatitis (AP) (Gerasimenko et al 2014).…”

A master stability function approach to cardiac alternans

“…In the present study, we investigate the linear stability of the synchronous network state as the strength of Ca 2+ diffusion is varied. Due to different intracellular morphologies and biochemical compositions, Ca 2+ generally diffuses more quickly in the cytosol than in the SR (but see Petersen et al (2017) for a different view). While diffusion of free Ca 2+ in the cytosol has been estimated to be 223 μm 2 s −1 (Allbritton et al 1992), Ca 2+ buffers reduce this value substantially (Smith et al 1996;Wagner and Keizer 1994).…”