Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Institute for Molecular Biotechnology (IMBA), Dr. Bohr-Gasse 3, 1030, Wien, Austria.
Pflugers Arch. 2021 Oct;473(10):1631-1639. doi: 10.1007/s00424-021-02612-4. Epub 2021 Aug 15.
Retinoblastoma is the most common malignant intraocular tumor in children. Y79 human retinoblastoma cells are in vitro models of retinal tumors used for drug screening. Undifferentiated Y79 cells originate from a primitive multi-potential neuroectodermal cell and express neuronal and glial properties. However, the nature of cellular heterogeneity in Y79 cells is unclear because functional methods to characterize neurons or glial cells have not been employed to Y79 cells. Here, we perform patch-clamp recordings to characterize electrophysiological properties in retinoblastoma cells. We identified a population of large-sized Y79 cells (i.e., giant cells, ~ 40-µm diameter), hyperpolarized resting membrane potential (-54 mV), and low input resistance (~ 600 MΩ), indicating electrically mature cells. We also found that giant Y79 cells contain increased density of T-type calcium channels. Finally, we found that T-type calcium channels are active only in giant cells suggesting that cancer treatments aimed to prevent calcium influx in retinoblastomas should be tested in giant cells.
视网膜母细胞瘤是儿童中最常见的恶性眼内肿瘤。Y79 人视网膜母细胞瘤细胞是用于药物筛选的视网膜肿瘤的体外模型。未分化的 Y79 细胞来源于原始多能神经外胚层细胞,并表达神经元和神经胶质特性。然而,由于尚未采用鉴定神经元或神经胶质细胞的功能方法,因此 Y79 细胞中细胞异质性的性质尚不清楚。在这里,我们进行膜片钳记录以表征视网膜母细胞瘤细胞的电生理特性。我们鉴定出一群大尺寸的 Y79 细胞(即巨细胞,直径约 40μm),超极化的静息膜电位(-54mV)和低输入电阻(约 600MΩ),表明电成熟的细胞。我们还发现,巨 Y79 细胞中 T 型钙通道的密度增加。最后,我们发现 T 型钙通道仅在巨细胞中活跃,这表明旨在防止钙流入视网膜母细胞瘤的癌症治疗方法应在巨细胞中进行测试。