Calcium flux mediated by purified inositol 1,4,5-trisphosphate receptor in reconstituted lipid vesicles is allosterically regulated by adenine nucleotides.
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 microM, 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.
Ferris
C D
CD
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Huganir
R L
RL
Snyder
S H
SH
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D006150:Guanine Nucleotides / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D008081:Liposomes; D051379:Mice; D008954:Models, Biological; D011510:Proteolipids / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear
D000227:Adenine Nucleotides; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D006150:Guanine Nucleotides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008081:Liposomes; D011510:Proteolipids; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; C020485:proteoliposomes; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium