This study was undertaken to examine the possible association of large-conductance calcium-activated potassium channels (BK(Ca) channels) and human retinal pigment epithelial (RPE) R-50 cell phagocytosis. The potential antioxidative effect of resveratrol in human RPE cells also was investigated. Cultured human RPE R-50cells were treated with hydrogen peroxide ( H(2)O(2), 10 microM, 20 min), meclofenamic acid (30 microM, 20 min), paxilline (100 nM, 20 min), or resveratrol (10 microM, 20 min), respectively. Meclofenamic acid (30 microM, 20 min) or resveratrol (10 microM, 20 min) was given after exposure to H(2)O(2) . Pretreatment with meclofenamic acid, resveratrol, or paxilline before H(2)O(2) exposure also was performed. Fluorescent latex beads then were fed for 4 h, and phagocytic function was assessed by flow cytometry. H(2)O(2) inhibited the phagocytic function of human RPE R-50 cells. The BK(Ca) channel inhibitor, paxilline, inhibited RPE phagocytosis, as did hyperoxide stress. The BK(Ca) channel opener, meclofenamic acid, prevented the damage caused by H(2)O(2) . Pretreatment with resveratrol also provided protection against damage caused by H(2)O(2) . However, further treatment with resveratrol or meclofenamic acid was not found to offer protection from H(2)O(2) exposure. In conclusion, the dietary antioxidant, resveratrol, significantly reduced oxidative damage on phagocytic function in human RPE R-50 cells. One of the underlying mechanisms might be linked to the activity of BK(Ca) channels in RPE cells.