THE ROLE OF ENDOPLASMIC-RETICULUM CALCIUM PUMPS DURING CYTOSOLIC CALCIUM SPIKING IN PANCREATIC ACINAR-CELLS

Many cell types show repetitive short lasting cytosolic calcium spikes with long interspike periods when stimulated with submaximal concentr ations of agonists linked to the phosphoinositide signaling pathway. I n pancreatic acinar cells these spikes have been shown to be evoked by constant levels of inositol trisphosphate through a mechanism of calc ium-induced calcium release and do not depend acutely on the presence of external calcium. However, the processes involved in the interspike period have remained unclear. Here we report that the endoplasmic ret iculum Ca2+-ATPases play a significant role, not only in resequesterin g calcium after a spike, but also in regulating the long interspike pe riod. Decreasing the activity of the endoplasmic reticulum calcium pum ps leads to shorter interspike intervals and thus higher spiking frequ encies, while the duration of each spike increases. The endoplasmic re ticulum Ca2+-ATPases are able to entirely suppress a response that can subsequently be evoked by partial inhibition of the pumps. This sugge sts that during the interspike period there is a considerable amount o f calcium released from intracellular stores, which is rapidly buffere d by the endoplasmic reticulum calcium pumps and the cytosolic calcium -binding proteins. A calcium spike will be initiated by calcium-induce d calcium release only when the buffering is saturated.