Labrakakis C, Patt S, Weydt P, Cervós-Navarro J, Meyer R, Kettenmann H
Department of Cellular Neurosciences, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
J Neuropathol Exp Neurol. 1997 Mar;56(3):243-54. doi: 10.1097/00005072-199703000-00003.
We studied the electrophysiological properties of cells from human glioblastomas obtained after surgery. The membrane currents were compared in cells of acute tissue slices and primary cultures using the whole cell mode of the patch-clamp technique. Very strikingly, in about a third of the tumor cells in situ and in vitro, depolarizing voltage steps elicited large, tetrodotoxin-sensitive inward currents with a threshold of about -30 mV, indicating the presence of voltage-gated sodium channels. In addition, three types of potassium currents, a delayed rectifying, an A-type, and an inward rectifying, were observed. Such a set of voltage-gated channels is characteristic for neurons. Indeed, in these glioblastoma cells, depolarizing current pulses in the current clamp mode were able to generate action potentials with properties similar to those observed in neurons. We interpret this finding as the ability of glioblastoma cells to acquire neuronlike properties but retain some glial features, since they still express markers typical for astrocytes and their precursors. The role of sodium channels in glioblastoma cells is unclear at this moment and needs further investigation. Our findings, however, imply that the tumor tissue can be intrinsically excitable and that neoplastic glial cells themselves may be an etiologic factor for epileptic seizures.
我们研究了手术后获取的人胶质母细胞瘤细胞的电生理特性。使用膜片钳技术的全细胞模式,对急性组织切片和原代培养细胞中的膜电流进行了比较。非常引人注目的是,在原位和体外的肿瘤细胞中,约三分之一的细胞在去极化电压阶跃时会引发大的、对河豚毒素敏感的内向电流,阈值约为 -30 mV,这表明存在电压门控钠通道。此外,还观察到三种类型的钾电流,即延迟整流钾电流、A型钾电流和内向整流钾电流。这样一组电压门控通道是神经元的特征。实际上,在这些胶质母细胞瘤细胞中,电流钳模式下的去极化电流脉冲能够产生与神经元中观察到的性质相似的动作电位。我们将这一发现解释为胶质母细胞瘤细胞具有获得类神经元特性但保留一些胶质细胞特征的能力,因为它们仍然表达星形胶质细胞及其前体典型的标志物。目前,钠通道在胶质母细胞瘤细胞中的作用尚不清楚,需要进一步研究。然而,我们的发现表明肿瘤组织可能具有内在兴奋性,并且肿瘤性胶质细胞本身可能是癫痫发作的一个病因。