COOKING WITH CALCIUM - THE RECIPES FOR COMPOSING GLOBAL SIGNALS FROM ELEMENTARY EVENTS

Recent studies have suggested that global intracellular Ca2+ signals a rise from the summation and coordination of subcellular elementary rel ease events (e.g., ''Ca2+ puffs''), although the modes of recruitment of such signals are unknown. In order to understand how cells utilize elementary Ca2+ release events, we imaged Ca2+ transients evoked throu gh the phosphoinositide pathway in HeLa cells using confocal microscop y. During the pacemaker phase leading to the global Ca2+ signal, eleme ntary Ca2+ release events were recruited in (1) frequency, (2) amplitu de, and (3) spatial domains. Since each digital elementary event contr ibutes to a small change of the analog cytosolic Ca2+ concentration, t he net effect of the advancement in the three domains is to drive the ambient Ca2+ concentration toward a threshold where the signal becomes regenerative, resulting in a global Ca2+ wave.