Fishman M C, Spector I
Proc Natl Acad Sci U S A. 1981 Aug;78(8):5245-9. doi: 10.1073/pnas.78.8.5245.
Quinine and quinidine have been evaluated with regard to their effects on the electrical activity of neuroblastoma cells. Under voltage-clamp conditions, we have found that quinine and quinidine block both the voltage-dependent and Ca2+-dependent K+ conductances. Blockage of the voltage-dependent K+ channel is manifest as an increase in the amplitude and in the duration of the action potential. Blockage of the Ca2+-dependent K+ channel in Na+-free (replaced by Tris) solutions containing 6.8 mM Ca2+ and tetraethylammonium ion or 4-aminopyridine (to block the voltage-dependent K+ current) is seen as a further prolongation of the Ca2+ action potential and diminution of the after-hyperpolarization. A critical role of the Ca2+-dependent K+ conductance in modulation of the rate and duration of trains of Ca2+ action potentials is shown by the use of low concentrations (5-40 microM) of quinine or quinidine, which diminish the Ca2+-dependent K+ conductance in a graded manner. After complete blockade of K+ currents, the peak Ca2+ currents are enhanced at all voltages, especially at values more positive than -30 mV, where a steady-state inward current appears as well. In this same voltage range, the decay of the Ca2+ current exhibits two time constants--that of the transient inward current, which is about 20 msec, and a much slower (approximately 2000 msec) component. It is suggested that neuroblastoma cells have two types of calcium channels--one which generates the Ca2+ action potential and a second, distinguished by activation at more depolarized levels and by a slow rate of inactivation, which underlies the calcium entry necessary to activate the Ca2+-dependent K+ conductance.
已对奎宁和奎尼丁对神经母细胞瘤细胞电活动的影响进行了评估。在电压钳制条件下，我们发现奎宁和奎尼丁可阻断电压依赖性和Ca2+依赖性钾离子电导。电压依赖性钾离子通道的阻断表现为动作电位幅度和持续时间的增加。在含有6.8 mM Ca2+和四乙铵离子或4-氨基吡啶（以阻断电压依赖性钾离子电流）的无钠（用Tris替代）溶液中，Ca2+依赖性钾离子通道的阻断表现为Ca2+动作电位的进一步延长和超极化后电位的减小。使用低浓度（5-40 microM）的奎宁或奎尼丁可显示Ca2+依赖性钾离子电导在调节Ca2+动作电位序列的速率和持续时间方面的关键作用，其以分级方式降低Ca2+依赖性钾离子电导。在完全阻断钾离子电流后，所有电压下的峰值Ca2+电流均增强，尤其是在比-30 mV更正的电位处，此时还会出现稳态内向电流。在相同的电压范围内，Ca2+电流的衰减表现出两个时间常数——瞬态内向电流的时间常数约为20毫秒，以及一个慢得多（约2000毫秒）的成分。有人提出神经母细胞瘤细胞有两种类型的钙通道——一种产生Ca2+动作电位，另一种在更去极化水平激活且失活速率缓慢，是激活Ca2+依赖性钾离子电导所需的钙内流的基础。
