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Ling Wang, Tie Li, Luo Lu; UV-Induced Corneal Epithelial Cell Death by Activation of Potassium Channels. Invest. Ophthalmol. Vis. Sci. 2003;44(12):5095-5101. doi: 10.1167/iovs.03-0590.
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purpose. The purpose of the present study is to determine the role of K+ channel activity as an early event in UV-induced corneal epithelial cell apoptosis.
method. Both cell-attached and nystatin-perforated patch-clamping were performed to record K+ channel activity in rabbit corneal epithelial (RCE) and primary cultured rabbit corneal epithelial (PRCE) cells exposed to UV irradiation. On exposure of corneal epithelial cells or intact corneas to UV-C irradiation or treatment of corneal epithelial cells with etoposide, cell apoptosis was determined by DNA fragmentation, ethidium bromide-acridine orange nuclear stain and TdT-mediated dUTP nick-end labeling (TUNEL).
results. In the present study, UV-irradiation–induced corneal epithelial cell apoptosis through activation of a K+ channel in the cell membrane was an early event in response to UV irradiation. UV-C irradiation (42 μJ/cm2) activated robust K+ channel activity in RCE and PRCE cells at both the single-channel and whole-cell levels, when measured with the cell-attached and nystatin-perforated patch clamps, respectively. Suppression of UV-irradiation–induced K+ channel activity with the specific K+ channel blocker 4-aminopurydine (4-AP) prevented UV-irradiation–induced apoptosis in the RCE and PRCE cells, loss of the superficial layer of corneal epithelium, and apoptosis in the basal layer corneal epithelium. However, suppression of K+ channel activity did not protect RCE and PRCE cells from etoposide, a topoisomerase II inhibitor, which induced cell death by bypassing the membrane. Furthermore, application of valinomycin, a K+ ionophore, to mimic the effect of mass activation of the K+ channel in RCE and PRCE cells caused cell apoptosis.
conclusions. The results indicate that UV irradiation induces superactivity of K+ channels in the membrane is an early event mediating signaling transduction and resulting in corneal epithelial cell death in response to UV irradiation.
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