Calcium flux mediated by purified inositol 1,4,5-trisphosphate receptor in reconstituted lipid vesicles is allosterically regulated by adenine nucleotides.

Abstract

When incorporated into lipid vesicles, the purified inositol 1,4,5-trisphosphate (IP3) receptor protein mediates 45Ca2+ flux. We observe a potent, selective allosteric regulation by ATP of IP3 actions on Ca2+ flux. The action of ATP is selective for adenine nucleotides with ADP and AMP less potent and GTP inactive. At 1-10 .mu.M, ATP increases maximal IP3-induced flux by 50% with no change in IP3 potency. The enhancing effect of ATP diminishes between 0.1 and 1 mM. Concentration-response curves are steep for both the increasing and the decreasing effects of ATP on IP3 actions, suggesting a physiological regulatory role of ATP in IP3-induced Ca2+ release. Diminishing local ATP concentrations coincident with filling of Ca2+ stores by the Ca2+-ATPase may enhance IP3 release of Ca2+, an effect that would decline as ATP returns to physiological levels. ATP regulation of Ca2+ release may also play a role in oscillations of intracellular Ca2+ concentration.