Kamleiter M, Hanemann C O, Kluwe L, Rosenbaum C, Wosch S, Mautner V F, Müller H W, Grafe P
Department of Physiology, University of Munich, Germany.
Glia. 1998 Nov;24(3):313-22.
Previous experimental observations indicate that inhibition of voltage-dependent K+ currents suppresses proliferation of normal Schwann cells. In the present study we tested the opposite relationship, i.e., whether Schwann cells from tumors with abnormally high rates of proliferation would have an increase in membrane K+ currents. Whole-cell membrane currents were studied in cultured cells from schwannomas of two neurofibromatosis type 2 (NF2) patients (n = 53), one patient with a sporadic schwannoma (n = 22), and two control subjects (n = 41). Five different types of voltage-dependent membrane currents were found in all of the Schwann cells tested. Membrane depolarization activated outward K+ and Cl- currents; quinidine was found to block the K+ current (IC50 approximately 1 microM), and NPPB reduced the Cl- current. Ba2+-sensitive inward rectifier K+ currents, fast Na+ currents, and a transient, inactivating K+ current were less frequently observed. On average, NF2 cells were found to have statistically significant higher membrane potential and larger non-inactivating K+ outward current as compared to controls. Electrophysiological parameters of Schwann cells from a sporadic schwannoma showed a tendency for larger outward currents; however, the difference did not reach statistical significance. Together the data support the suggestion of a possible link between K+ outward current and proliferation of Schwann cells.
先前的实验观察表明,抑制电压依赖性钾离子电流可抑制正常雪旺细胞的增殖。在本研究中,我们测试了相反的关系,即增殖率异常高的肿瘤中的雪旺细胞其膜钾离子电流是否会增加。我们研究了来自两名2型神经纤维瘤病(NF2)患者(n = 53)、一名散发型神经鞘瘤患者(n = 22)的神经鞘瘤以及两名对照受试者(n = 41)的培养细胞中的全细胞膜电流。在所有测试的雪旺细胞中发现了五种不同类型的电压依赖性膜电流。膜去极化激活外向钾离子和氯离子电流;发现奎尼丁可阻断钾离子电流(IC50约为1 microM),而NPPB可降低氯离子电流。较少观察到钡离子敏感的内向整流钾离子电流、快速钠离子电流和一种瞬时失活的钾离子电流。平均而言,与对照组相比,发现NF2细胞具有统计学上显著更高的膜电位和更大的非失活外向钾离子电流。散发型神经鞘瘤的雪旺细胞的电生理参数显示出外向电流有增大的趋势;然而,差异未达到统计学显著性。这些数据共同支持了钾离子外向电流与雪旺细胞增殖之间可能存在联系的观点。