Hegg C C, Miletic V
Department of Comparative Biosciences and the Environmental Toxicology Center, University of Wisconsin, Madison 53706-1102, USA.
Brain Res. 1997 Oct 24;772(1-2):63-70. doi: 10.1016/s0006-8993(97)00839-1.
Rat pheochromocytoma (PC12) cells were exposed to lead acetate (0, 10, 25 and 50 microM) in their growth media for up to 12 weeks. High-threshold voltage-gated calcium currents were recorded each week from nerve growth factor-differentiated PC12 cells using the whole-cell patch-clamp technique. Chronic exposure for 1 month did not modify peak or sustained calcium current amplitudes in lead-treated cells when compared to sister control cultures. Two month exposure to 25 and 50 microM significantly increased peak and sustained calcium current amplitudes, while 10 microM had little effect. During the third month of exposure, peak and sustained calcium current amplitudes remained increased in the cells exposed to 25 and 50 microM lead acetate. By the end of the second month of exposure to 25 and 50 microM lead acetate, the voltage at which maximal current amplitude was attained shifted from + 10 mV to 0 mV. The observed effects of toxicologically relevant lead concentrations on high-threshold calcium currents in chronically exposed mammalian cells provide further support for the notion that at least one cellular target of the heavy metal's neurotoxic action may be the voltage-gated calcium channel.
将大鼠嗜铬细胞瘤（PC12）细胞在其生长培养基中暴露于醋酸铅（0、10、25和50微摩尔）长达12周。每周使用全细胞膜片钳技术从神经生长因子分化的PC12细胞中记录高阈值电压门控钙电流。与对照姐妹培养物相比，1个月的慢性暴露并未改变铅处理细胞中的峰值或持续钙电流幅度。暴露于25和50微摩尔两个月显著增加了峰值和持续钙电流幅度，而10微摩尔的影响很小。在暴露的第三个月，暴露于25和50微摩尔醋酸铅的细胞中峰值和持续钙电流幅度仍然增加。到暴露于25和50微摩尔醋酸铅的第二个月末，达到最大电流幅度的电压从+10毫伏移至0毫伏。在慢性暴露的哺乳动物细胞中，毒理学相关铅浓度对高阈值钙电流的观察效应为以下观点提供了进一步支持，即重金属神经毒性作用的至少一个细胞靶点可能是电压门控钙通道。
