Stimulation of oscillatory uterine contraction by the PCB mixture aroclor 1242 may involve increased [Ca2+](i) through voltage-operated calcium channels

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants as sociated with spontaneous abortion and shortened gestation length in women and animals. In previous studies, we showed that PCB mixtures and noncoplan ar ortho-substituted PCB congeners increased contractions in pregnant rat u terus, In the present study, we hypothesized that the PCB mixture Aroclor 1 242 (A1242) stimulates oscillatory uterine contraction in pregnant uterus b y increasing intracellular calcium concentration ([Ca2+](i)), Pretreatment of uterine strips with ryanodine or thapsigargin, to deplete specific intra cellular calcium stores, did not prevent the increased frequency of oscilla tory contraction due to 50 mu M A1242, whereas thapsigargin effectively blo cked carbachol-induced stimulation of uterine contraction. However, 100 mu M A1242 was unable to increase contraction in the absence of extracellular calcium or in the presence of the voltage-operated L-type calcium channel b locker nifedipine, A1242 (100 mu M) was observed to partially depolarize th e cell membrane of myometrial cells from pregnant rats, as measured with a potential-sensitive carbocyanine dye. Changes of [Ca2+](i) were monitored i n single myometrial cells loaded with the fluorescent calcium-sensitive pro be fura-2, Cells exposed to 100 mu M A1242 showed a delayed and sustained i ncrease of [Ca2+](i), and this increase was completely blocked in the absen ce of extracellular calcium or the presence of nifedipine. Therefore, the d ata suggest that depolarization of the cell membrane by A1242 enabled myome trial cells to increase [Ca2+](i) through activation of voltage-operated ca lcium channels, and the increased [Ca2+](i) consequently stimulated contrac tion of uterine smooth muscle, (C) 1999 Academic Press.