Differential effects of 20 non-dioxin-like PCBs on basal and depolarization-evoked intracellular calcium levels in PC12 cells.

Non–dioxin-like polychlorinated biphenyls (NDL-PCBs) are environmental pollutants that are well known for their neurotoxic effects. Numerous in vitro studies reported PCB-induced increases in the basal intracellular calcium concentration ([Ca 21 ]i), and in vivo NDL-PCB neurotoxicity appears at least partly mediated by these disturbances. However, effects of NDL-PCBs on depolarizationevoked calcium influx are poorly investigated, and effects of several congeners, including PCB53, on calcium homeostasis are still unknown. We therefore studied the effects of 20 selected NDLPCBs on basal and depolarization-evoked [Ca 21 ]i in fura-2–loaded PC12 cells using single-cell fluorescence microscopy. The results demonstrate that hexa- and heptachlorobiphenyls (with the exception of PCB136) were unable to affect basal and depolarizationevoked [Ca 21 ]i. However, most tri- and tetrachlorinated as well as some pentachlorinated NDL-PCBs (at 1 and 10mM) increased basal [Ca 21 ]i during a 15-min exposure. The increase in basal [Ca 21 ]i, which differed in kinetics for the different congeners, depended partly on influx of extracellular calcium and calcium release from the endoplasmic reticulum. Importantly, all tested tri- and tetrachlorinated biphenyls and some pentachlorinated NDL-PCBs (PCB95, PCB100, and PCB104) reduced depolarization-evoked [Ca 21 ]i, with PCB51 and PCB53 being most potent (near complete inhibition at 1mM). The reduction in depolarization-evoked calcium influx depended on the exposure duration but not on the foregoing PCB-induced increase in basal [Ca 21 ]i. The inhibition of