CYCLIC ADP-RIBOSE MODULATES CA2+ RELEASE CHANNELS FOR ACTIVATION BY PHYSIOLOGICAL CA2+ ENTRY IN BULLFROG SYMPATHETIC NEURONS

Although Ca2+-induced Ca2+ release (CICR) via ryanodine receptors has been found to occur in intact neurons, little is known about the physi ological processes that regulate it. We studied the effects of cyclic ADP-ribose (cADPR) on CICR in cultured bullfrog sympathetic neurons by fura-2 fluorescence recording and patch-clamp techniques. cADPR appli ed through a patch pipette augmented action potential- or depolarizing pulse-induced rises in intracellular Ca2+ without a change in Ca2+ en try initiating the responses, but not in the presence of ryanodine. Li kewise, cADPR enhanced a single or oscillatory rise(s) in intracellula r Ca2+ induced by caffeine. These results strongly suggest that cADPR tan be an endogenous modulator of ryanodine receptors in neurons.