Cyclic ADP-ribose activates caffeine-sensitive calcium channels from sea urchin egg microsomes

Adenosine 5'-cyclic diphosphoribose [cyclic ADP-ribose (cADPR)], a metabolite of NAD+ that promotes Ca2+ release from sea urchin egg homogenates and microsomal fractions, has been proposed to act as an endogenous agonist of Ca2+ release in sea urchin eggs. We describe experiments showing that a microsomal fraction isolated from Tetrapigus nyger sea urchin eggs displayed Ca(2+)-selective single channels with conductances of 155.0 +/- 8.0 pS in asymmetric Cs+ solutions and 47.5 +/- 1.1 pS in asymmetric Ca2+ solutions. These channels were sensitive to stimulation by Ca2+, ATP, and caffeine, but not inositol 1,4,5-trisphosphate, and were inhibited by ruthenium red. The channels were also activated by cADP-ribose in a Ca(2+)-dependent fashion. Calmodulin and Mg2+, but not heparin, modulated channel activity in the presence of cADP-ribose. We propose that these Ca2+ channels constitute the intracellular Ca(2+)-induced Ca2+ release pathway that is activated by cADP-ribose in sea urchin eggs.