Buffer kinetics shape the spatiotemporal patterns of IP3-evoked Ca2+ signals

Ca 2+ liberation through inositol 1,4,5-trisphosphate receptors (IP 3 Rs) plays a universal role in cell regulation, and specificity of cell signalling is achieved through the spatiotemporal patterning of Ca 2+ signals. IP 3 Rs display Ca 2+ -induced Ca 2+ release (CICR), but are grouped in clusters so that regenerative Ca 2+ signals may remain localized to individual clusters, or propagate globally between clusters by successive cycles of Ca 2+ diffusion and CICR. We used confocal microscopy and photoreleased IP 3 in Xenopus oocytes to study how these properties are modulated by mobile cytosolic Ca 2+ buffers. EGTA (a buffer with slow ‘on-rate’) speeded Ca 2+ signals and ‘balkanized’ Ca 2+ waves by dissociating them into local signals. In contrast, BAPTA (a fast buffer with similar affinity) slowed Ca 2+ responses and promoted ‘globalization’ of spatially uniform Ca 2+ signals. These actions are likely to arise through differential effects on Ca 2+ feedback within and between IP 3 R clusters, because Ca 2+ signals evoked by influx through voltage-gated channels were little affected. We propose that cell-specific expression of Ca 2+ -binding proteins with distinct kinetics may shape the time course and spatial distribution of IP 3 -evoked Ca 2+ signals for specific physiological roles.