Figure 1.

Model for regulation of capacitative calcium entry channels by IP₃ receptors. Agonist activation of a surface membrane receptor (R), perhaps through a heterotrimeric G-protein (G), activates phospholipase C (PLC), leading to the production of the calcium-mobilizing messenger, IP₃. IP₃ releases calcium from a critical endoplasmic reticulum store. The fall in luminal calcium in this store causes a conformational change in an IP₃ receptor that interacts with a TRP subunit of the capacitative calcium entry channel, causing it to open. A signaling complex containing the PLC, TRP, and IP₃ receptor may require an as yet uncharacterized scaffolding protein, perhaps similar to InaD. The close spatial arrangement of this signaling complex results in a constant supply of IP₃ from basal PLC activity for the IP₃ receptor, such that IP₃ levels are not normally limiting; rather, it is depletion of calcium from the specific intracellular store that provides the critical signal for channel activation.