Hydroxylated PCB induces Ca2+ oscillations and alterations of membrane potential in cultured cortical cells.
Polychlorinated biphenyls (PCBs) are known as environmental pollutants that may cause adverse health effects. Although some congeners have been shown to affect brain development or function, the molecular mechanisms mediating their toxicity are not yet fully understood. Since signal transduction via intracellular Ca(2+) is crucial for neuronal development and plasticity, we investigated the effect of PCBs on Ca(2+) homeostasis and membrane potential in cultured mouse cortical cells. Acute exposure to hydroxylated PCB 106 [4(OH)-2',3,3',4',5'-pentachlorobiphenyl, OH-PCB 106, 0.1 microM] caused recurring Ca(2+) oscillations that were classified into three prototypes. Although extracellular Ca(2+) deprivation significantly reduced the oscillations, 54% of the cells still showed different patterns of oscillations or gradual increase in the intracellular Ca(2+) concentration, indicating possible involvement of multiple Ca(2+) channels in a cell-specific manner. Such a possibility was further confirmed by differential responses to several channel/receptor blockers, including nifedipine, ryanodine, xestospongine and tetrodotoxin. Although all chemicals had partial inhibition action in different subsets of neurons, nifedipine blocked the OH-PCB 106 action in the largest subpopulation of cells and with the greatest magnitude. Ryanodine also blocked the action with a similar magnitude, but in a smaller subpopulation of cells. Moreover, OH-PCB 106 induced depolarization of the plasma membrane in all the recorded cells. Taken together, our results indicate that OH-PCB 106 alters membrane potential as well as Ca(2+) dynamics in part by inducing extracellular influx and/or intracellular release of Ca(2+). These mechanisms may be responsible for their neurotoxicity.
Londoño
Marina
M
Department of Integrative Physiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi Maebashi, Gunma, 371-8511 Japan.
Shimokawa
Noriaki
N
Miyazaki
Wataru
W
Iwasaki
Toshiharu
T
Koibuchi
Noriyuki
N
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000032:analysis; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005456:Fluorescent Dyes / Q000032:analysis; D016257:Fura-2 / Q000032:analysis; D006706:Homeostasis / Q000187:drug effects; D006900:Hydroxylation; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D019579:Neocortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*
D002614:Chelating Agents; D004785:Environmental Pollutants; D005456:Fluorescent Dyes; D011078:Polychlorinated Biphenyls; D002118:Calcium; D016257:Fura-2