Increases in the intracellular Ca concentrations are often a result of IP activation. When a ligand binds to a G protein-coupled receptor (GPCR) that is coupled to a Gq heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC isozyme PLC-β, which results in the cleavage of PIP into IP and DAG.
If a receptor tyrosine kinase (RTK) is involved in activating the pathway, the isozyme PLC-γ has tyrosine residues that can become phosphorylated upon activation of an RTK, and this will activate PLC-γ and allow it to cleave PIP into DAG and IP. This occurs in cells that are capable of responding to growth factors such as insulin, because the growth factors are the ligands responsible for activating the RTK.
IP (also abbreviated Ins(1,4,5)P is a soluble molecule and is capable of diffusing through the cytoplasm to the ER, or the sarcoplasmic reticulum (SR) in the case of muscle cells, once it has been produced by the action of PLC. Once at the ER, IP is able to bind to the Ins(1,4,5)P receptor Ins(1,4,5)PR which is a ligand-gated Ca channel that is found on the surface of the ER. The binding of IP (the ligand in this case) to Ins(1,4,5)PR triggers the opening of the Ca channel, and thus release of Ca into the cytoplasm. In heart muscle cells this increase in Ca activates the ryanodine receptor-operated channel on the SR, results in further increases in Ca through a process known as calcium-induced calcium release. IP may also activate Ca channels on the cell membrane indirectly, by increasing the intracellular Ca concentration.