Stimulation of Oscillatory Uterine Contraction by the PCB Mixture Aroclor 1242 May Involve Increased [Ca2+]ithrough Voltage-Operated Calcium Channels

Abstract

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants associated with spontaneous abortion and shortened gestation length in women and animals. In previous studies, we showed that PCB mixtures and noncoplanarortho-substituted PCB congeners increased contractions in pregnant rat uterus. In the present study, we hypothesized that the PCB mixture Aroclor 1242 (A1242) stimulates oscillatory uterine contraction in pregnant uterus by increasing intracellular calcium concentration ([Ca2+]i). Pretreatment of uterine strips with ryanodine or thapsigargin, to deplete specific intracellular calcium stores, did not prevent the increased frequency of oscillatory contraction due to 50 μM A1242, whereas thapsigargin effectively blocked carbachol-induced stimulation of uterine contraction. However, 100 μM A1242 was unable to increase contraction in the absence of extracellular calcium or in the presence of the voltage-operated L-type calcium channel blocker nifedipine. A1242 (100 μM) was observed to partially depolarize the cell membrane of myometrial cells from pregnant rats, as measured with a potential-sensitive carbocyanine dye. Changes of [Ca2+]iwere monitored in single myometrial cells loaded with the fluorescent calcium-sensitive probe fura-2. Cells exposed to 100 μM A1242 showed a delayed and sustained increase of [Ca2+]i, and this increase was completely blocked in the absence of extracellular calcium or the presence of nifedipine. Therefore, the data suggest that depolarization of the cell membrane by A1242 enabled myometrial cells to increase [Ca2+]ithrough activation of voltage-operated calcium channels, and the increased [Ca2+]iconsequently stimulated contraction of uterine smooth muscle.