IP3 receptors

A regenerative process whereby an intracellular Ca2+ channel (IP3 receptor or Ryanodine receptor) is itself stimulated by Ca2+, allowing thereby Ca2+ to promote its own release from intracellular stores. 

IP3 Receptor Ryanodine Receptor Non-selective Cations Channels TRP Channels... 

Local and transient Ca2+ increases that propagate throughout the cytosol of individual cells in the form of waves. Ca2+ waves are generated by a positive feedback activation of Ca2+ release from the intracellular Ca2+ stores through ryanodine receptors or inositol IP3 receptors. 

Inositol 1,4,5-trisphosphate (IP3) receptors are intracellular cation channels. They are expressed in most cells and predominantly within the membranes of the endoplasmic reticulum. They mediate release of Ca2+ from intracellular stores by the many receptors that stimulate IP3 formation. 

IP3 Receptors. Figure 1 Interplay between Ca2+ channels. Ca2+ signals are initiated when an extracellular stimulus (red) directly opens a Ca2+ channel in the plasma membrane or indirectly, via a signalling pathway (green), opens an intracellular Ca2+ channel. Ca2+ signals may then be propagated across the cell by Ca2+-induced Ca2+ release mediated by IP3R or RyR. 

IP3 Receptors. Figure 2 Key structural features of IP3 receptors. The key domains are shown in the central block. The upper structures show the suppressor domain (PDB accession code, 1XZZ) and the IBC (1N4K) with its (red) and p (blue) domains. A proposed structure for the pore region is shown below, with the selectivity filter shown in red only two of the four subunits are shown. The lowest panel shows reconstructed 3D structures of IP3R1 viewed (left to right) from ER lumen, the cytosol and in cross-section across the ER membrane (reproduced with permission from [4]). 

Taylor CW, Laude AJ (2002) IP3 receptors and their regulation by calmodulin and cytosolic Ca2+. Cell Calcium 32 321-334... 

IP3 receptor associated cGMP kinase substrate of 130 kDa that is present in all smooth muscles and platelets. It s phosphorylation decreases calcium release from intracellular EP3-sensitive stores. 

The molecular weight of isolated IP3 receptor protein is about 225 kDa but the actual receptor is apparently a tetramer. The IP3 receptor is slightly smaller in size than the ryanodine receptor which is also a tetramer. Also, like the ryanodine receptor, Ca ion binding has a synergistic effect on the IP3 receptor. As one might expect, these two receptors have a large sequence homology. There is not much... 

Another popular assay for GPCR activation is to measure the increase in intracellular Ca2+ that occurs upon activation. GPCRs on the cell surface produce inositol triphosphate (IP3) via the action of Phospholipase C (PLC). IP3 stimulates calcium channels called IP3 receptors on the endoplasmic reticulum, which raise... 

Membrane activities IP3-receptor Certain kinases (calmodulin) C-2 domains... 

Capacitative Ca2+ entry is the predominant mode of regulated Ca2+ entry in nonexcitable cells but it also occurs in a number of excitable cell types. This pathway of Ca2+ entry is usually associated with the activation of phospholipase C, which mediates the formation of IP3 (see Ch. 20). Intracellular application of IP3 mimics the ability of hormones and neurotransmitters to activate calcium ion entry, and activation of calcium ion entry by hormones and neurotransmitters can be blocked by intracellular application of low-molecular-weight heparin, which potently antagonizes IP3 binding to its receptor. There is considerable evidence for the presence of an IP3 receptor in the plasma membrane of some cells types. 1(1,3,4,5)P4, a product of IP3 phosphorylation, has been shown in some cells to augment this action of IP3 in activating PM calcium ion entry, but in others IP3 alone is clearly sufficient. 

Two general mechanisms have been considered by which a depleted intracellular Ca2+ pool might communicate with the plasma membrane [4]. There is evidence that the IP3 receptor is associated with the cytoskeleton, and this association may tether the IP3 receptor to the plasma membrane. Depletion of intracellular calcium stores might cause a conformational change in the IP3 receptor, which could be conveyed to the plasma membrane via the cytoskeleton or by a more direct protein-protein interaction. Alternatively, signaling could occur... 

Periodic temporal and spatial patterns of Ca2+ signaling give rise to calcium oscillations and waves. As discussed above, the IP3 receptor is subject to complex and only... 

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