Inositol trisphosphate receptors: Ca2+-modulated intracellular Ca2+ channels.
The three subtypes of inositol trisphosphate (InsP3) receptor expressed in mammalian cells are each capable of forming intracellular Ca2+ channels that are regulated by both InsP3 and cytosolic Ca2+. The InsP3 receptors of many, though perhaps not all, tissues are biphasically regulated by cytosolic Ca2+: a rapid stimulation of the receptors by modest increases in Ca2+ concentration is followed by a slower inhibition at higher Ca2+ concentrations. Despite the widespread occurrence of this form of regulation and the belief that it is an important element of the mechanisms responsible for the complex Ca2+ signals evoked by physiological stimuli, the underlying mechanisms are not understood. Both accessory proteins and Ca2+-binding sites on InsP3 receptors themselves have been proposed to mediate the effects of cytosolic Ca2+ on InsP3 receptor function, but the evidence is equivocal. The effects of cytosolic Ca2+ on InsP3 binding and channel opening, and the possible means whereby the effects are mediated are discussed in this review.
Taylor
C W
CW
Department of Pharmacology, Tennis Court Road, Cambridge CB2 1QJ, UK. cwt1000@cam.ac.uk
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium