Twenty Years of Calcium Imaging: Cell Physiology to Dye For

Overall Ca²⁺homeostasis in pancreatic acinar cell. The top two traces show [Ca²⁺] in the lumen of the ER and the cytosol, before, during, and after maximal ACh stimulation. Below are shown representations of the state of the four principal Ca²⁺ transporters in four situations: 1) Rest, before start of stimulation. Small fluxes of Ca²⁺ through Ca²⁺ release channels in the ER (for simplicity only the IP₃ receptor is shown), ER Ca²⁺ pumps (SERCA), the plasma membrane Ca²⁺ pump (PMCA), and the store-operated Ca²⁺ entry pathway (also known as capacitative Ca²⁺ entry; CCE). Fluxes across both plasma and ER membranes are in equilibrium. 2) Steady-state stimulated situation. After the initial release of Ca²⁺ from the ER, both Ca²⁺ pumps (SERCA and PMCA) are now fully activated and the store-operated Ca²⁺ entry path is also open, due to the reduced [Ca²⁺]_ER. 3) Immediately after cessation of ACh stimulation. The IP₃ receptor channels have closed and the SERCA pump can now refill the ER via Ca²⁺ entering through the plasma membrane. The PMCA is no longer activated because [Ca²⁺]_i has quickly returned to the basal level. 4) Normal Ca²⁺ gradients have been restored to the resting basal level. [Adapted from (90).]