Overview: The inositol 1,4,5-trisphosphate receptors (IP3R) are ligand-gated Ca2+ release channels on intracellular Ca2+ store sites (such as the endoplasmic reticulum). They are responsible for the mobilization of intracellular Ca2+ stores and play an important role in intracellular Ca2+ signalling in a wide variety of cell types. Three different gene products (types I–III) have been isolated, which assemble as large tetrameric structures. IP3Rs are closely associated with certain proteins: calmodulin and FKBP (and calcineurin via FKBP). They are phosphorylated by PKA, PKC, PKG and CaMKII.
| Nomenclature | IP3R1 | IP3R2 | IP3R3 |
|---|---|---|---|
| Other names | INSP3R1 | INSP3R2 | INSP3R3 |
| Ensembl ID | ENSG00000150995 | ENSG00000123104 | ENSG00000096433 |
| Endogenous activators | Ins(1,4,5)P3 (nM–µM), cytosolic Ca2+ (<750 µM), cytosolic ATP (<mM) | Ins(1,4,5)P3 (nM–µM), cytosolic Ca2+ (nM) | Ins(1,4,5)P3 (nM–µM), cytosolic Ca2+ (nM) |
| Pharmacological activators | InsP3 analogues including Ins(2,4,5)P3, adenophostin A (nM) | InsP3 analogues including Ins(2,4,5)P3, adenophostin A (nM) | – |
| Antagonists | Xestospongin C (µM), caffeine (mM), phosphatidylinositol 4,5-bisphosphate (µM), heparin (µg·mL−1), decavanadate (µM), calmodulin at high cytosolic Ca2+ | Heparin (µg·mL−1), decavanadate (µM) | Heparin (µg·mL−1), decavanadate (µM) |
| Functional characteristics | Ca2+: (PBa/PK∼ 6) single-channel conductance: ∼70 pS (50 mM Ca2+) | Ca2+: single-channel conductance: ∼70 pS (50 mM Ca2+), ∼390 pS (220 mM Cs+) | Ca2+: single-channel conductance: ∼88 pS (55 mM Ba2+) |
The absence of a modulator of a particular isoform of receptor indicates that the action of that modulator has not been determined, not that it is without effect.
Glossary
Abbreviation:
- FKBP
FK506-binding protein
Further Reading
Balla T (2009). Regulation of Ca2+ entry by inositol lipids in mammalian cells by multiple mechanisms. Cell Calcium45: 527–534.
Berridge MJ, Lipp P, Bootman MD (2000). The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol1: 11–21.
Bolton TB (2006). Calcium events in smooth muscles and their interstitial cells: physiological roles of sparks. J Physiol570: 5–11.
Bootman MD, Berridge MJ, Roderick HL (2002). Calcium signalling: more messengers, more channels, more complexity. Curr Biol12: R563–R565.
Bosanac I, Michikawa T, Mikoshiba K, Ikura M (2004). Structural insights into the regulatory mechanism of IP3 receptor. Biochim Biophys Acta1742: 89–102.
Bultynck G, Sienaert I, Parys JB, Callewaert G, De Smedt H, Boens N et al. (2003). Pharmacology of inositol trisphosphate receptors. Pflugers Arch445: 629–642.
Choe CU, Ehrlich BE (2006) The inositol 1,4,5-triphosphate receptor (IP3R) and its regulators: sometimes good and sometimes bad team work. Sci STKE2006 (363): re15.
Foskett JK, White C, Cheung KH, Mak DO (2007). Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev87: 593–658.
Mikoshiba K (2007). IP3 receptor/Ca2+ channel from discovery to new signaling concepts. J Neurochem102: 1426–1446.
Mikoshiba K (2007). The IP3 receptor/Ca2+ channel and its cellular function. Biochem Soc Symp74: 9–22.
Nahorski SR (2006). Pharmacology of intracellular signalling pathways. Br J Pharmacol147 (Suppl. 1): S38–S45.
Patel S, Joseph SK, Thomas AP (1999). Molecular properties of inositol 1,4,5-trisphosphate receptors. Cell Calcium25: 247–264.
Patterson RL, Boehning D, Snyder SH (2004). Inositol 1,4,5-triphosphate receptors as signal integrators. Annu Rev Biochem73: 437–465.
Taylor CW, Traynor D (1995). Calcium and inositol trisphosphate receptors. J Membr Biol145: 109–118.
Verkhratsky A (2005) Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev85: 201–279.
Vermassen E, Parys JB, Mauger J-P (2004). Subcellular distribution of the inositol 1,4,5-triphosphate receptors: functional relevance and molecular determinants. Biol Cell96: 3–17.