The Ca(2+) signals that control almost every cellular activity are generated by regulating Ca(2+) transport, usually via Ca(2+)-permeable channels, across the plasma membrane or the membranes of intracellular organelles. The most widespread and best understood of the intracellular Ca(2+) channels are inositol trisphosphate receptors (IP(3)R) and ryanodine receptors, most of which are expressed in the endoplasmic or sarcoplasmic reticulum. However, accumulating evidence suggests physiological roles for many additional Ca(2+) channels in both ER and other intracellular organelles. Interactions between these channels, whether mediated by Ca(2+) itself or interactions between proteins, is a recurrent feature of the Ca(2+) signals evoked by physiological stimuli. We focus on two specific examples, clustering of IP(3)Rs and NAADP (nicotinic acid dinucleotide phosphate)-evoked Ca(2+) release from endo-lysosomes, to illustrate the diversity of Ca(2+) channels and the interplay between them.
