Activation of a novel non-selective cation channel by alloxan and H2O2 in the rat insulin-secreting cell line CRI-G1.
1. Alloxan and its auto-oxidation product hydrogen peroxide (H2O2) irreversibly depolarize insulinoma cells by opening a non-selective cation channel. The channel opened is characterized by a linear current-voltage relation with a conductance of approximately 70 pS and very slow kinetics (of the order of seconds). 2. Cells are protected against the alloxan-induced channel opening and consequent cell depolarization by the presence of H2O2 and hydroxyl radical scavengers. 3. The free radical-activated non-selective cation channel is not operative in isolated patches but can be activated by the application of beta-NAD+ to the cytoplasmic aspect of the membrane.
Herson
P S
PS
Department of Biomedical Sciences, University of Aberdeen, UK.
Ashford
M L
ML
D000496:Alloxan / Q000494:pharmacology*; D000818:Animals; D016764:Cell Polarity / Q000187:drug effects; D003545:Cysteine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009536:Niacinamide / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D009536:Niacinamide; D000496:Alloxan; C038983:1,3-dimethylthiourea; D006861:Hydrogen Peroxide; D013890:Thiourea; D003545:Cysteine