Ligand-induced generation of intracellular calcium ([Ca 2+] i) signals in nonexcitable cells involves activation of phospholipase C and generation of the Ca 2+-mobilizing messenger, inositol 1, 4, 5-trisphosphate (IP 3). IP 3 acts by binding to a specific receptor–ion channel on the endoplasmic reticulum (ER) activating the Ca 2+-permeable channel and thus causing the release of stored Ca 2+ to the cytoplasm. This release of Ca 2+ is closely followed by an influx of Ca 2+ into the cell across the plasma membrane (PM). The signal for activation of the PM channels does not come from the receptors or their associated G proteins, nor from IP 3, but appears to be a consequence of the fall of Ca 2+ within the ER Ca 2+ stores (