In pancreatic acinar cells, the physiological cytosolic Ca²⁺ signals consist mostly of repetitive local Ca²⁺ spikes confined to the apical granular region. These signals can be induced by physiological concentrations of acetylcholine (ACh) or cholecystokinin (CCK). The Ca²⁺ spikes are due to short-lasting openings of Ca²⁺ release channels in apical extensions of the endoplasmic reticulum (ER), which project into the granular region (Petersen et al. 2001). The Ca²⁺ released into the cytosol of the granular pole mostly stays in the apical area due to a mitochondrial firewall surrounding the granular region (Tinel et al. 1999). The local apical Ca²⁺ spikes elicit not only exocytosis, but also fluid secretion through opening of Ca²⁺-activated Cl^– channels localized specifically in the apical plasma membrane (Park et al. 2001). During physiological CCK stimulation, some of the local Ca²⁺ spikes trigger global Ca²⁺ waves. Global Ca²⁺ waves are generated by a complex interplay between at least three separate intracellular Ca²⁺ release channels controlled by inositol trisphosphate, cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate (Cancela et al. 2002) and depend on the process of Ca²⁺-induced Ca²⁺ release (Solovyova et al. 2002).

The resting free Ca²⁺ concentration in the ER store is about 100Ð300 µM and depends on the balance between the passive leak and the resting active uptake mediated by the Ca²⁺ pump. The main determinant of the rate of ER Ca²⁺ pumping is the Ca²⁺ concentration in the ER lumen (Petersen et al. 2001; Solovyova et al. 2002). Experiments with local Ca²⁺ uncaging in the ER lumen have shown directly the ability of Ca²⁺ to move quickly inside the ER over considerable distances (~10 µm) (Petersen et al. 2001). Ca²⁺ released from the ER terminals in the granular pole can therefore quickly be replenished by Ca²⁺ drawn from the bulk of the ER store in the basal region.

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