Near‐visible ultraviolet light induces a novel ubiquitous calcium‐permeable cation current in mammalian cell lines

1 We studied the immediate and short‐term effects of UV light in the near‐visible range at the cellular and membrane level using the whole‐cell patch‐clamp technique in combination with digital fluorescence imaging. 2 Illumination with monochromatic UVA light (340‐380 nm) induced a sustained non‐saturable increase in membrane conductance dependent on wavelength and light intensity in several different mammalian cell types including RBL, mast, HEK, PC12 and 3T3 cells. 3 The current was non‐selective for cations and permeable to Ca2+, but was inhibited by trivalent cations and was not due to the activation of an endogenous ion channel. We termed this novel current ILiNC for light‐induced non‐selective cation current. 4 A similar current was evoked by chemical peroxidants such as hydrogen peroxide and tert‐butylhydroperoxide, but not by cytosolic oxidized glutathione. 5 The free‐radical scavengers tocopherol (vitamin E) and ascorbic acid (vitamin C) significantly reduced the UV light effect. 6 The generation of the current was membrane delimited since it could be induced by the same UVA treatment in cell‐free membrane patches showing a similar wavelength dependence. 7 These results suggest that ILiNC is activated by UVA light‐induced generation of free radicals acting through lipid or protein peroxidation, and may represent a ubiquitous mechanism by which Na+ and Ca2+ can enter cells after phototoxic or free radical‐induced membrane damage.

[1]  T. Whiteside,et al.  Activation of Raf by ionizing radiation , 1996, Nature.

[2]  S. J. Elliott,et al.  Oxidized glutathione mediates cation channel activation in calf vascular endothelial cells during oxidant stress. , 1996, The Journal of physiology.

[3]  L. Zon,et al.  Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis , 1996, Nature.

[4]  S. J. Elliott,et al.  Oxidant stress activates a non‐selective cation channel responsible for membrane depolarization in calf vascular endothelial cells. , 1996, The Journal of physiology.

[5]  H. Gies,et al.  SOLAR UVR EXPOSURES OF THREE GROUPS OF OUTDOOR WORKERS ON THE SUNSHINE COAST, QUEENSLAND , 1995 .

[6]  R. Lavker,et al.  QUANTITATIVE ASSESSMENT OF CUMULATIVE DAMAGE FROM REPETITIVE EXPOSURES TO SUBERYTHEMOGENIC DOSES OF UVA IN HUMAN SKIN , 1995, Photochemistry and photobiology.

[7]  D. Godar,et al.  SPECTRAL DEPENDENCE OF UV‐INDUCED IMMEDIATE AND DELAYED APOPTOSIS: THE ROLE OF MEMBRANE AND DNA DAMAGE , 1995, Photochemistry and photobiology.

[8]  R. Tyrrell,et al.  Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Godar,et al.  NON‐NUCLEAR DAMAGE AND CELL LYSIS ARE INDUCED BY UVA, BUT NOT UVB OR UVC, RADIATION IN THREE STRAINS OF L5178Y CELLS , 1993, Photochemistry and photobiology.

[10]  R. Penner,et al.  A GTP-dependent step in the activation mechanism of capacitative calcium influx. , 1993, The Journal of biological chemistry.

[11]  E. Aizenman,et al.  The modulation of N‐methyl‐D‐aspartate receptors by redox and alkylating reagents in rat cortical neurones in vitro. , 1993, The Journal of physiology.

[12]  G. Matthews,et al.  Ca2+ and Mn2+ influx through receptor-mediated activation of nonspecific cation channels in mast cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[13]  M. Karin,et al.  The mammalian ultraviolet response is triggered by activation of src tyrosine kinases , 1992, Cell.

[14]  S. Hayashi,et al.  Cytosolic calcium increase in coronary endothelial cells after H2O2 exposure and the inhibitory effect of U78517F , 1992, British journal of pharmacology.

[15]  R. Schnellmann.  Intracellular calcium chelators and oxidant-induced renal proximal tubule cell death. , 1991, Journal of biochemical toxicology.

[16]  L. Dubertret,et al.  UVA-induced lipid peroxidation in cultured human fibroblasts. , 1991, Biochimica et biophysica acta.

[17]  G. Stark,et al.  The effect of ionizing radiation on lipid membranes. , 1991, Biochimica et biophysica acta.

[18]  Sirshendu Chatterjee,et al.  Membrane lipid peroxidation by UV‐A: mechanism and implications , 1990, Biotechnology and applied biochemistry.

[19]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[20]  T. Jacks,et al.  Sunburn and p53 in the onset of skin cancer , 1994, Nature.

[21]  M. P. Cortés,et al.  Lipid peroxidation and loss of potassium from red blood cells produced by phototoxic quinolones. , 1992, Toxicology.