Friel D D, Tsien R W
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, California 94305-5426.
J Neurosci. 1994 Jul;14(7):4007-24. doi: 10.1523/JNEUROSCI.14-07-04007.1994.
This study describes a Ca2+ store in fura-2-loaded bullfrog sympathetic neurons that modulates [Ca2+]i responses elicited by either depolarization or Ca2+ release from a caffeine- and ryanodine-sensitive store. This store is insensitive to caffeine and ryanodine, but is sensitive to the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). The FCCP-sensitive store slows both the rise in [Ca2+]i during stimulation (apparently by accumulating Ca2+ from the cytosol) and the recovery following stimulation (by releasing the accumulated Ca2+ into the cytosol). For a fixed level of depolarization, recovery is slowed to an extent that depends on stimulus duration. [Ca2+]i imaging shows that these effects are prominent in the soma but not in growth cones. Ca2+ uptake by the FCCP-sensitive store appears to be strongly [Ca2+]i dependent, since it becomes influential only when [Ca2+]i approaches approximately 500 nM. Therefore, this store may specifically influence [Ca2+]i during moderate and strong stimulation. The effect of the store on responses to depolarization can be accounted for by a simple three-compartment scheme consisting of the extracellular medium, the cytosol, and a single internal store with a [Ca2+]i-dependent uptake mechanism resembling the mitochondrial Ca2+ uniporter. The store's effect on responses to caffeine-induced Ca2+ release can be accounted for by including a second internal compartment to represent the caffeine-sensitive store. While the identity of the FCCP-sensitive store is unknown, its sensitivity to FCCP is consistent with a mitochondrial pool. It is suggested that by modulating the temporal properties of [Ca2+]i following stimulation, the FCCP-sensitive store may influence the degree of activation of intracellular [Ca2+]i-dependent processes.
本研究描述了在负载fura - 2的牛蛙交感神经元中的一种钙离子储存库，它可调节由去极化或从对咖啡因和兰尼碱敏感的储存库释放钙离子所引发的细胞内钙离子浓度（[Ca2+]i）反应。该储存库对咖啡因和兰尼碱不敏感，但对质子载体羰基氰化物对三氟甲氧基苯腙（FCCP）敏感。FCCP敏感的储存库在刺激期间减缓了[Ca2+]i的升高（显然是通过从细胞质中积累钙离子）以及刺激后的恢复过程（通过将积累的钙离子释放到细胞质中）。对于固定水平的去极化，恢复的减缓程度取决于刺激持续时间。[Ca2+]i成像显示，这些效应在细胞体中很显著，但在生长锥中不明显。FCCP敏感的储存库对钙离子的摄取似乎强烈依赖于[Ca2+]i，因为只有当[Ca2+]i接近约500 nM时它才会产生影响。因此，该储存库可能在中度和强烈刺激期间特异性地影响[Ca2+]i。该储存库对去极化反应的影响可以通过一个简单的三室模型来解释，该模型由细胞外介质、细胞质和一个具有类似于线粒体钙离子单向转运体的[Ca2+]i依赖性摄取机制的单一内部储存库组成。该储存库对咖啡因诱导的钙离子释放反应的影响可以通过纳入第二个内部隔室来表示对咖啡因敏感的储存库来解释。虽然FCCP敏感的储存库的身份尚不清楚，但其对FCCP的敏感性与线粒体池一致。有人提出，通过调节刺激后[Ca2+]i的时间特性，FCCP敏感的储存库可能会影响细胞内[Ca2+]i依赖性过程的激活程度。
