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 Ca(2+)-refilling mechanisms of the stores.
DeLisle
S
S
Veterans Affairs Medical Center, Iowa City, Iowa, USA.
Mayr
G W
GW
Welsh
M J
MJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000737:chemistry / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D013329:Structure-Activity Relationship; D014981:Xenopus
D007295:Inositol Phosphates; D008345:Manganese; D002118:Calcium