Cui Y, Galione A, Terrar D A
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
Biochem J. 1999 Sep 1;342 ( Pt 2)(Pt 2):269-73.
Actions of photoreleased cADP-ribose (cADPR), a novel regulator of calcium-induced calcium release (CICR) from ryanodine-sensitive stores, were investigated in cardiac myocytes. Photoreleased cADPR caused an increase in the magnitude of whole-cell calcium transients studied in mammalian cardiac ventricular myocytes (both guinea-pig and rat) using confocal microscopy). Approx. 15 s was required following photorelease of cADPR for the development of its maximal effect. Photoreleased cADPR also increased the frequency of calcium 'sparks', which are thought to be elementary events which make up the whole-cell calcium transient, and were studied in rat myocytes, but had little or no effect on spark characteristics (amplitude, rise time, decay time and distance to half amplitude). The potentiating effects of photoreleased cADPR on both whole-cell transients and the frequency of calcium sparks were prevented by cytosolic application of the antagonist 8-amino-cADPR (5 microM). These experiments, therefore, provide the first evidence in any cell type for an effect of cADPR on calcium sparks, and are the first to show the actions of photoreleased cADPR on whole-cell calcium transients in mammalian cells. The observations are consistent with the effects of cADPR in enhancing the calcium sensitivity of CICR from the sarcoplasmic reticulum in cardiac ventricular myocytes, leading to an increase in the probability of occurrence of calcium sparks and to an increase in whole-cell calcium transients. The slow time-course for development of the full effect on whole-cell calcium transients might be taken to indicate that the influence of cADPR on CICR may involve complex molecular interactions rather than a simple direct action of cADPR on the ryanodine-receptor channels.
在心肌细胞中研究了光释放的环二磷酸腺苷核糖（cADPR）的作用，cADPR是一种从兰尼碱敏感储存库中释放钙引起钙释放（CICR）的新型调节剂。使用共聚焦显微镜在哺乳动物心室肌细胞（豚鼠和大鼠）中研究发现，光释放的cADPR导致全细胞钙瞬变幅度增加。cADPR光释放后大约需要15秒才能产生最大效应。光释放的cADPR还增加了钙“火花”的频率，钙“火花”被认为是构成全细胞钙瞬变的基本事件，在大鼠心肌细胞中进行了研究，但对火花特征（幅度、上升时间、衰减时间和半幅度距离）几乎没有影响。通过胞质应用拮抗剂8-氨基-cADPR（5 microM）可阻止光释放的cADPR对全细胞瞬变和钙火花频率的增强作用。因此，这些实验首次在任何细胞类型中提供了cADPR对钙火花有作用的证据，并且首次展示了光释放的cADPR对哺乳动物细胞全细胞钙瞬变的作用。这些观察结果与cADPR增强心室肌细胞肌浆网CICR钙敏感性的作用一致，导致钙火花发生概率增加以及全细胞钙瞬变增加。对全细胞钙瞬变产生完全效应的缓慢时间进程可能表明，cADPR对CICR的影响可能涉及复杂的分子相互作用，而不是cADPR对兰尼碱受体通道的简单直接作用。
