Cyclic ADP-ribose Enhances Coupling between Voltage-gated Ca2+ Entry and Intracellular Ca2+ Release

cADP-ribose potentiates cytosolic Ca2+ elevation and Ca2+ entry via L-type voltage-activated Ca2+ channels in NG108-15 neuronal cells

“…cADPR, if present, together with increased Ca# + , may enhance CICR, as shown in Scheme 1(B). This action of cADPR for [Ca# + ] i increase by VACC activation was already suggested in previous studies [13,14]. The present results, however, are new, in that L-type VACCs could be involved in this process in neurons.…”

“…cADPR is reported to potentiate the depolarization-induced [Ca# + ] i increase in bullfrog sympathetic neurons [13] and NG108-15 neuroblastomaiglioma hybrid cells [14]. These results led us to consider the possibility that cADPR could be a messenger Abbreviations used : [Ca 2 + ] i , cytoplasmic free Ca 2 + concentration ; RyR, ryanodine receptor ; RyR-1, -2, -3, type-1, -2 and -3 RyR, respectively ; CICR, Ca 2 + -induced Ca 2 + release ; ADPR, ADP-ribose ; cADPR, cADP-ribose ; VACC, voltage-activated Ca 2 + channel ; fura-2 AM, fura-2 acetoxymethyl ester ; 8-Br-cADPR, 8-bromo-cADPR ; [Ca 2 + ] o , extracellular Ca 2 + concentration ; PKA, cAMP-dependent protein kinase.…”

“…Thus, the questions addressed here are whether or not VACCs are potentiated after cADPR-dependent activation of RyRs and, if so, which type (L or N) of VACC is involved. To pursue these issues, we used differentiated NG108-15 cells which possess low-and highthreshold VACCs [15] and RyRs that are sensitive to caffeine [14,16]. In this preparation, we have found that β-NAD + and cADPR function as modulators of the M-type K + channel [17] and have characterized ADP-ribosyl cyclase activity, which converts cADPR from β-NAD + [18].…”

An Antagonist of cADP-ribose Inhibits Arrhythmogenic Oscillations of Intracellular Ca2+ In Heart Cells

“…ADP-ribosyl cyclase activity has been identified in rat cardiac myocytes (7), and intracellular levels of cADPR have been estimated to be of the order of 200 nM (11). Furthermore, cADPR has been reported to enhance CICR in a number of preparations, including guinea pig heart cells (12), sea urchin eggs (33,34), and neuronal cells (5,(35)(36)(37). This would support the hypothesis that suppression of Ca 2ϩ oscillations (provoked by isoproterenol and ouabain) by 8-amino-cADPR and 8-bromo-cADPR is because of antagonism of the actions of endogenous cADPR, which sensitizes the CICR mechanism to Ca 2ϩ .…”

Complex interactions between skeletal muscle ryanodine receptor and dihydropyridine receptor proteins

“…Gaz+ is released from intracellular Cal+ stores through RyR by Ca*+-induced Ca2+ release and activation by ligands such as cyclic ADP ribose (Empson and Galione, 1997;Mothet et al, 1998).…”