IP3-gated Ca2+channels

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. 

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]. 

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)... 

The addition of CaBPs can directly activate the IP3-R in a Ca2+-dependent manner, via interaction with the N-terminus region of the receptor. This raises the possibility that CaBPs can act on IP3-Rs to potentiate the Ca2+ signals that arise from other sources, e.g. ligand-gated ion channels. 

In many cells, phosphoinositide signaling leads to an elevation in intracellular calcium levels through the release of calcium from intracellular stores in response to IP3-dependent gating of channels in the endoplasmic epithelium (Ch. 20). It is not known if IP3 plays a critical role in TRC transduction, but such a role would be consistent with recent findings that a Ca2+-activated cation channel, TRPM5, is essential for normal sweet, bitter and umami taste function [49,66-69],... 

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... 

---