Panfoli I, Burlando B, Viarengo A
Istituto Policattedra di Chimica Biologica, Università di Genova, V. le Benedetto XV 1, Genova, 16132, Italy.
Biochem Biophys Res Commun. 1999 Apr 2;257(1):57-62. doi: 10.1006/bbrc.1999.0405.
Cyclic ADP-ribose (cADPR) elicits calcium-induced calcium release (CICR) in a variety of cell types. We studied the effect of cADPR on Ca2+ release in muscle cells by incubating SR vesicles from scallop (Pecten jacobaeus) adductor muscle in the presence of the Ca2+ tracer fluo-3. Exposure of SR to cADPR (20 microM) produced Ca2+ release, which was a function of free [Ca2+] in a range between about 150 and 1000 nM, indicating an involvement of ryanodine-sensitive Ca2+ channels. This Ca2+ release was not significantly enhanced by calmodulin (7 micrograms/ml), but it was enhanced by equimolar addition of noncyclic ADPR. Also, the Ca2+ release elicited by cADPR/ADPR was a function of free [Ca2+] in a range between about 150 and 3000 nM, over which Ca2+ was inhibitory. cADPR self-inactivation was observed at low free [Ca2+] (about 150 nM), but it tended to disappear upon [Ca2+] elevation (about 250 nM). Caffeine or ryanodine induced a Ca2+ release which was ruthenium red (2.5 microM) sensitive at low [Ca2+]. However, the Ca2+ release induced by either ryanodine or cADPR was no longer ruthenium red sensitive when free [Ca2+] was increased. Based on these data, a model is proposed for Ca2+ signaling in muscle cells, where a steady-state cADPR level would trigger Ca2+ release when free [Ca2+] does reach a threshold slightly above its resting level, hence producing cascade RyR recruitment along SR cisternae from initial Ca2+ signaling sites.
环磷酸腺苷核糖（cADPR）在多种细胞类型中引发钙诱导的钙释放（CICR）。我们通过在钙示踪剂氟-3存在的情况下孵育扇贝（Pecten jacobaeus）闭壳肌的肌浆网囊泡，研究了cADPR对肌肉细胞中Ca2+释放的影响。将肌浆网暴露于cADPR（20微摩尔）会产生Ca2+释放，这是游离[Ca2+]在约150至1000纳摩尔范围内的函数，表明ryanodine敏感的Ca2+通道参与其中。这种Ca2+释放并未被钙调蛋白（7微克/毫升）显著增强，但等摩尔添加非环磷酸腺苷核糖会增强它。此外，cADPR/ADPR引发的Ca2+释放是游离[Ca2+]在约150至3000纳摩尔范围内的函数，在此范围内Ca2+具有抑制作用。在低游离[Ca2+]（约150纳摩尔）时观察到cADPR自我失活，但随着[Ca2+]升高（约250纳摩尔）它往往会消失。咖啡因或ryanodine诱导的Ca2+释放在低[Ca2+]时对钌红（2.5微摩尔）敏感。然而，当游离[Ca2+]增加时，ryanodine或cADPR诱导的Ca2+释放不再对钌红敏感。基于这些数据，提出了一个肌肉细胞中Ca2+信号传导的模型，其中当游离[Ca2+]确实达到略高于其静息水平的阈值时，稳态cADPR水平会触发Ca2+释放，从而从初始Ca2+信号位点沿肌浆网池产生级联的兰尼碱受体募集。
