Type III InsP3 receptor channel stays open in the presence of increased calcium

• Published in: Nature (London) 1998-11, Vol.396 (6706), p.81-84
• Main Authors: Hagar, Robert E., Burgstahler, Angela D., Nathanson, Michael H., Ehrlich, Barbara E.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Allosteric Regulation; Animals; Biochemistry; Biological and medical sciences; Calcium; Calcium - metabolism; Calcium Channels - metabolism; Calcium Signaling; Cell Line; Cell membranes. Ionic channels. Membrane pores; Cell structures and functions; Cellular biology; Cytoplasm - metabolism; Dogs; Endoplasmic Reticulum - metabolism; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Inositol 1,4,5-Trisphosphate - metabolism; Inositol 1,4,5-Trisphosphate Receptors; letter; Molecular and cellular biology; multidisciplinary; Rats; Receptors, Cytoplasmic and Nuclear - metabolism; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/23954

The inositol 1,4,5-trisphosphate receptor (InsP 3 R) is the main calcium(Ca 2+ ) release channel in most tissues. Three isoforms have been identified 1 , 2 , 3 , 4 , 5 , 6 , but only types I and II InsP 3 R have been characterized 7 , 8 . Here we examine the functional properties of the type III InsP 3 R because this receptor is restricted to the trigger zone from which Ca 2+ waves originate 9 , 10 , 11 and it has distinctive InsP 3 -binding properties 12 , 13 . We find that type III InsP 3 R forms Ca 2+ channels with single-channel currents that are similar to those of type I InsP 3 R; however, the open probability of type III InsP 3 R isoform increases monotonically with increased cytoplasmic Ca 2+ concentration, whereas the type I isoform has a bell-shaped dependence on cytoplasmic Ca 2+ . The properties of type III InsP 3 R provide positive feedback as Ca 2+ is released; the lack of negative feedback allows complete Ca 2+ release from intracellular stores. Thus, activation of type III InsP 3 R in cells that express only this isoform results in a single transient, but global, increase in the concentration of cytosolic Ca 2+ . The bell-shaped Ca 2+ -dependence curve of type I InsP 3 R is ideal for supporting Ca 2+ oscillations, whereas the properties of type III InsP 3 R are better suited to signal initiation.