Inositol phosphate structural requisites for Ca²⁺ influx

To understand how inositol phosphates (InsP) cause Ca²⁺ influx, we injected 37 highly purified compounds containing a total of 49 InsP positional isomers into Xenopus oocytes. The eight InsP that stimulated Ca²⁺ influx were those that had the highest potency at releasing intracellular Ca²⁺, indicating that their common target was the inositol 1,4,5-trisphosphate [Ins(1,4,5)P₃] receptor. To cause Ca²⁺ influx, these InsP had to be injected in a much higher concentration than the minimal concentration required to release intracellular Ca²⁺. Such high InsP concentrations could inhibit ongoing oscillatory intracellular Ca²⁺ release. In addition, we found that InsPs could not elicit further intracellular Ca²⁺ release during the course of Ca²⁺ influx. Our data are consistent with the 'capacitative Ca²⁺ entry' hypothesis, which states that InsP stimulate Ca²⁺ influx by depleting the InsP-sensitive intracellular Ca²⁺ store. In this context, we would suggest that to deplete the InsP- sensitive intracellular Ca²⁺ store, InsP may have to be present in a sufficiently high concentration to override the oscillatory Ca²⁺-refilling mechanisms of the stores.