Unique inactivation properties of NAADP-sensitive Ca²⁺ release

Ca²⁺ mobilization from intracellular stores constitutes an important mechanism for generating cytoplasmic Ca²⁺ signals. Inositol trisphosphate (InsP₃) and ryanodine receptors are the two families of intracellular Ca²⁺ release channels that have been identified, which may be regulated by separate intracellular messengers, InsP₃ and cyclic adenosine 5′-diphosphate ribose, respectively. A third molecule, nicotinic acid adenine dinucleotide phosphate (NAADP), has recently been recognized as a potent Ca²⁺ releasing agent in sea urchin eggs and microsomes. We now report that non-releasing concentrations of NAADP fully and irreversibly inactivate the NAADP-sensitive Ca²⁺ release mechanism. This phenomenon occurred both in intact sea urchin eggs and in homogenates and is not shared by either InsP₃ or cyclic adenosine 5′-diphosphate ribose. The novel properties of this Ca²⁺ release mechanism, giving a one-shot Ca²⁺ release, may be suited to irreversible cellular events.