IP3 receptors Ca2+ channel

Mikoshiba K IP3 receptor/Ca2+ channel from discovery to new signaling concepts. J Neurochem 2007 102 1426. [PMID 17697045]... 

Intracellular, ER-located, ligand-gated Ca2+ channels include the inositol-1,4,5-triphosphate (IP3) receptor, the ryanodine receptor (RyR), the NAADP receptor and the sphingolipid receptor [157-159]. The IP3 receptor Ca2+ channel is opened by IP3 generated as a result of G protein-(or RTK)-mediated PLC activation [159]. 

Some olfactory neurons may use a second transduction mechanism. They have receptors coupled through G proteins to PLC rather than to adenylyl cyclase. Signal reception in these cells triggers production of IP3 (Fig. 12-19), which opens IP3-gated Ca2+ channels in the ciliary membrane. Influx of Ca2+ then depolarizes the ciliary membrane and generates a receptor potential or regulates Ca2+-dependent enzymes in the olfactory pathway. 

At the neuromuscular junction, ACh activates the nicotinic AChR, resulting in a Na+ influx and a depolarisation. This event generates an action potential which spreads along the membrane via voltage-gated Na+ channels (discussed in above) Muscle cells and neurons possess Ca2+ channels [57], the so-called ryanodine reptors (regulated by the alkaloid ryanodine Table 10), and IP3-sensitive Ca2+ channels. In skeletal muscle cells, ryanodine receptors are located in the sarcoplasmic reticulum (SR)... 

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. 

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. 

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... 

Voltage-dependent Na+, K+, Ca2+ channels Ca2+-dependent potassium channels Enzymes and other proteins involved in the regulation of second messengers G proteins Phospholipases Adenylyl cyclases Guanylyl cyclases Phosphodiesterases IP3 receptor Protein kinases... 

This can be illustrated by known interactions between the cAMP and Ca2+ pathways. A first messenger that initially activates the cAMP pathway would be expected to exert secondary effects on the Ca2+ pathway at many levels via phosphorylation by PKA. First, Ca2+ channels and the inositol trisphosphate (IP3) receptor will be phosphorylated by PKA to modulate intracellular concentrations of Ca2+. Second, phospholipase C (PLC) is a substrate for PKA, and its phosphorylation modulates intracellular calcium concentrations, via the generation of IP3) as well as the activity of PKC, via the generation of DAG, and several types of CAMK. Similarly, the Ca2+ pathway exerts potent effects on the cAMP pathway, for example, by activating or inhibiting the various forms of adenylyl cyclase expressed in mammalian tissues (see Ch. 21). 

Kiselyov K, Mignery GA, Zhu MX, Muallem S 1999 The N-terminal domain of the IP3 receptor gates store-operated hTrp3 channels. Mol Cell 4 423-429 Lee HC 2000 NAADP An emerging calcium signaling molecule. J Membr Biol 173 1 -8 Lin S, Fagan KA, Li K-X, Shaul PW, Cooper DMF, Rodman DM 2000 Sustained endothelial nitric-oxide synthase activation requires capacitative Ca2+ entry. J Biol Chem 275 17979-17985... 

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