[As2O3-induced permeability transition pore opening in mitochondria depends on Ca2+].

OBJECTIVE: To explore the mechanism of arsenite-induced permeability transition pore (PTP) opening and the role of Ca(2+). in As(2)O(3)-induced PTP opening. METHOD: The mitochondria were prepared from Wistar rat liver and mitochondrial swelling was assessed spectrophotometrically at 540 nm to evaluate PTP opening. The membrane potential of the mitochondria was measured with fluorescence spectrophotometry. RESULTS: PTP opening was induced with 10 micromol/L As(2)O(3) in the presence of 10 micromol/L Ca(2+), and the absorbance at 540 nm of the mitochondria did not decrease in response to exclusive treatment with 10 micromol/L As(2)O(3), or to 10 micromol/L As(2)O(3) plus 10 micromol/L Ca(2+) treatment with 0.5 mmol/L EGTA pretreatment. Treatment with As(2)O(3) at 0, 5, 10 and 20 micromol/L in the presence of 50, 20, 10 and 5 micromol/L Ca(2+), respectively, resulted in decreased absorbance at 540 nm of the mitochondria. CONCLUSION: Ca(2+) mediates As(2)O(3)-induced PTP opening. As(2)O(3) lowers Ca(2+) threshold necessary for eliciting PTP opening and thereby regulates cell apoptosis.