Distasi C, Torre M, Antoniotti S, Munaron L, Lovisolo D
Istituto Nazionale per la Fisica della Materia, and Dipartimento di Biologia Animale e dell' Uomo, Università di Torino, Italy.
Eur J Neurosci. 1998 Jul;10(7):2276-86. doi: 10.1046/j.1460-9568.1998.00239.x.
Basic fibroblast growth factor (bFGF/FGF2) exhibits widespread biological activities in the nervous system. However, little is known about the cascade of intracellular events that links the activation of its tyrosine kinase receptors to these effects. Here we report that, in ciliary ganglion neurons from chick embryo, this trophic factor significantly enhanced neuronal survival. The percentage of surviving neurons was reduced when intracellular calcium was chelated by adding a membrane-permeable BAPTA ester to the culture medium, while antagonists of L- and N-type voltage-dependent calcium channels were ineffective. The ionic signals in response to bFGF stimulation have been studied using cytofluorimetric and patch-clamp techniques. In single-cell Fura-2 measurements, bFGF elicited a long lasting rise of the cytosolic calcium concentration that was dependent on [Ca2+]o. In whole-cell experiments, we observed a reversible depolarization of the membrane resting potential and an inward cationic current. Single channel experiments, performed in the cell-attached configuration, provide evidence for the activation of two families of Ca2+-permeable cationic channels. Moreover, inositol 1,4,5-trisphosphate opens channels with similar properties, suggesting that this cytosolic messenger can be responsible for the calcium influx induced by bFGF.
碱性成纤维细胞生长因子（bFGF/FGF2）在神经系统中具有广泛的生物学活性。然而，对于将其酪氨酸激酶受体的激活与这些效应联系起来的细胞内事件级联反应，我们知之甚少。在此，我们报道，在鸡胚睫状神经节神经元中，这种营养因子能显著提高神经元的存活率。当通过向培养基中添加可透过细胞膜的BAPTA酯来螯合细胞内钙时，存活神经元的百分比降低，而L型和N型电压依赖性钙通道拮抗剂则无效。我们使用细胞荧光测定法和膜片钳技术研究了对bFGF刺激的离子信号。在单细胞Fura-2测量中，bFGF引起胞质钙浓度的持久升高，这依赖于细胞外钙离子浓度（[Ca2+]o）。在全细胞实验中，我们观察到膜静息电位的可逆去极化和内向阳离子电流。在细胞贴附模式下进行的单通道实验，为激活两类钙离子通透阳离子通道提供了证据。此外，肌醇1,4,5-三磷酸打开具有相似特性的通道，表明这种胞质信使可能是bFGF诱导钙内流的原因。
