Differential regulation of ER Ca2+ uptake and release rates accounts for multiple modes of Ca2+-induced Ca2+ release.

The ER is a central element in Ca(2+) signaling, both as a modulator of cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and as a locus of Ca(2+)-regulated events. During surface membrane depolarization in excitable cells, the ER may either accumulate or release net Ca(2+), but the conditions of stimulation that determine which form of net Ca(2+) transport occurs are not well understood. The direction of net ER Ca(2+) transport depends on the relative rates of Ca(2+) uptake and release via distinct pathways that are differentially regulated by Ca(2+), so we investigated these rates and their sensitivity to Ca(2+) using sympathetic neurons as model cells.