Cytoplasmic calcium oscillations: A two pool model

Abstract

Cytosolic calcium oscillations induced by a wide range of agonists, particularly those which stimulate phosphoinositide metabolism, are the result of a periodic release of stored calcium. The formation of inositol 1,4,5 trisphosphate (Ins(1,4,5)P 3) seems to play an important role because it can initiate this periodic behaviour when injected or perfused into a variety of cells. A two pool model has been developed to explain how Ins(1,4,5)P 3 sets up these calcium oscillations. It is proposed that Ins(1,4,5)P 3 acts through its specific receptor to create a constant influx of primer calcium (Ca 2+ p) made up of calcium released from the Ins(1,4,5)P 3-sensitive pool (ISCS) together with an influx of external calcium. This Ca 2+ p fails to significantly elevate cytosolic calcium because it is rapidly sequestered by the Ins(1,4,5)P 3-insensitive (IICS) stores of calcium distributed throughout the cytosol. Once the latter have filled, they are triggered to release their stored calcium through a process of calcium-induced calcium release to give a typical calcium spike (Ca 2+ s). In many cells, each Ca 2+ s begins at a discrete initiation site from which it then spreads through the cell as a wave. The two pool model can account for such waves if it is assumed that calcium released from one IICS diffused across to excite its neighbours thereby setting up a self-propagating wave based on calcium-induced calcium release.