The versatility of Ca(2+) as an intracellular messenger derives largely from the spatial organization of cytosolic Ca(2+) signals, most of which are generated by regulated openings of Ca(2+)-permeable channels. Most Ca(2+) channels are expressed in the plasma membrane (PM). Others, including the almost ubiquitous inositol 1,4,5-trisphosphate receptors (IP(3)R) and their relatives, the ryanodine receptors (RyR), are predominantly expressed in membranes of the sarcoplasmic or endoplasmic reticulum (ER). Targeting of these channels to appropriate destinations underpins their ability to generate spatially organized Ca(2+) signals. All Ca(2+) channels begin life in the cytosol, and the vast majority are then functionally assembled in the ER, where they may either remain or be dispatched to other membranes. Here, by means of selective examples, we review two issues related to this trafficking of Ca(2+) channels via the ER. How do cells avoid wayward activity of Ca(2+) channels in transit as they pass from the ER via other membranes to their final destination? How and why do some cells express small numbers of the archetypal intracellular Ca(2+) channels, IP(3)R and RyR, in the PM?
