KINETIC-PROPERTIES OF NICOTINIC-ACID ADENINE-DINUCLEOTIDE PHOSPHATE-INDUCED CA2+ RELEASE

Three endogenous molecules have now been shown to release Ca2+ in the sea urchin egg: inositol trisphosphate (InsP(3)), cyclic adenosine 5'- diphosphate ribose (cADPR), and nicotinic acid adenine dinucleotide ph osphate (NAADP) a derivative of NADP, While the mechanism through whic h the first two molecules are able to release Ca2+ is established and well characterized with InsP, and cADPR-activating InsP(3) and ryanodi ne receptors, respectively, the newly described NAADP has been shown t o release Ca2+ via an entirely different mechanism, The most striking feature of this novel Ca2+ release mechanism is its inactivation, sinc e subthreshold concentrations of NAADP are able to fully and irreversi bly desensitize the channel, In the present study we have investigated the fast kinetics of activation and inactivation of NAADP-induced Ca2 + release, NAADP was found to release Ca2+ in a biphasic manner, and s uch release was preceded by a pronounced latent period, which was inve rsely dependent on concentration, Moreover, the kinetic features of NA ADP-induced Ca2+ release were not altered by pretreatment with low con centrations of NAADP, although the extent of Ca2+ release was greatly affected, Our data suggest that the inactivation of NAADP-induced Ca2 release is an all-or-none phenomenon, and while some receptors have b een fully inactivated, those that remain sensitive to NAADP do so with out any change in kinetic features.