Calcium is a ubiquitous signalling molecule, known to control a vast array of cellular processes. In order to retain stimulus fidelity, the cell encodes the increases in intracellular calcium in the form of oscillations that are regulated both temporally and spatially. Here, we review recent work, using the pancreatic acinar cell as a model system, on the mechanisms employed to generate and modulate cytosolic Ca 2+ signals, and the technical advances that have made these studies possible.
We have compared calcium mobilization by Ins(1,4,5) P 3 (IP 3 ), cADP-ribose (cADPR) and nicotinic acid–adenosine dinucleotide phosphate (NAADP) from the envelope of isolated nuclei with the calcium signalling in intact isolated pancreatic acinar cells. Ca 2+ uptake and release were studied with calcium-sensitive fluorescent probes. In the present study, we have shown that all calcium messengers induce Ca 2+ release from the nuclear envelope. Pre-treatment of nuclei with thapsigargin completely abolished the responses to the calcium messengers, indicating that Ca 2+ stores in isolated nuclei are thapsigargin-sensitive. Using different pharmacological tools, we show that Ca 2+ release from pancreatic nuclei is unlikely to occur from stores other than those with endoplasmic reticulum characteristics. We conclude that all three calcium messengers can release Ca 2+ from pancreatic acinar nuclear stores, as previously shown for IP 3 and cADPR. It would appear that NAADP releases Ca 2+ from the same IP 3 - and cADPR-sensitive stores with endoplasmic reticulum characteristics.