TYPE-III INSP(3) RECEPTOR-CHANNEL STAYS OPEN IN THE PRESENCE OF INCREASED CALCIUM

The inositol 1,4,5-trisphosphate receptor (InsP(3)R) is the mai(n) cal cium(Ca2+) release channel in most tissues. Three isoforms have been i dentified(1-6), but only types I and II InsP(3)R have been characteriz ed(7,8). Here we examine the functional properties of the type In InsP (3)R because this receptor is restricted to the trigger zone from whic h Ca2+ waves originate(9-11) and it has distinctive InsP(3)-binding pr operties(12,13). We find that type III InsP(3)R forms Ca2+ channels wi th 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 increase s monotonically with increased cytoplasmic Ca2+ concentration, whereas the type I isoform has a bell-shaped dependence on cytoplasmic Ca2+. The properties of type III InsP(3)R provide positive feedback as Ca2is released; the lack of negative feedback allows complete Ca2+ releas e from intracellular stores. Thus, activation of type III InsP(3)R in cells that express only this isoform results in a single transient, bu t global, increase in the concentration of cytosolic Ca2+. The bell-sh aped Ca2+-dependence awe of type I InsP(3)R is ideal for supporting Ca 2+ oscillations, whereas the properties of type III InsP(3)R are bette r suited to signal initiation.