Ins(1,4,5)P 3 diffuses rapidly within the cytosol to interact with endoplasmic reticulum (ER)-located Ins(1,4,5)P 3 receptors (Ins(1,4,5)P 3Rs), which are channels that release Ca 2+ from the ER lumen to generate the initial Ca 2+ signal phase 149. Following ligand binding to phospholipase C (PLC)-coupled receptors (right), the second messengers inositol-1,4,5-trisphosphate (Ins(1,4,5) P 3) and diacylglycerol (DAG) are generated through breakdown of phosphatidylinositol-4,5- bisphosphate (PtdIns(4,5)P 2). Resting cells (left) maintain cytosolic Ca 2+ in the nM range through sarcoplasmic reticulum Ca 2+ ATPase (SERCA) and plasma membrane Ca 2+ ATPase (PMCA) pumps.
The events that maintain cellular Ca 2+ signalling during homeostasis are shown in part a of the figure.
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