Diphtheria toxin-induced channels in Vero cells selective for monovalent cations.
Ion fluxes associated with translocation of diphtheria toxin across the surface membrane of Vero cells were studied. When cells with surface-bound toxin were exposed to low pH to induce toxin entry, the cells became permeable to Na+, K+, H+, choline+, and glucosamine+. There was no increased permeability to Cl-, SO4(-2), glucose, or sucrose, whereas the uptake of 45Ca2+ was slightly increased. The influx of Ca2+, which appears to be different from that of monovalent cations, was reduced by several inhibitors of anion transport and by verapamil, Mn2+, Co2+, and Ca2+, but not by Mg2+. The toxin-induced fluxes of N+, K+, and protons were inhibited by Cd2+. Cd2+ also protected the cells against intoxication by diphtheria toxin, suggesting that the open cation-selective channel is required for toxin translocation. The involvement of the toxin receptor is discussed.
Sandvig
K
K
Institute for Cancer Research, Norwegian Radium Hospital, Oslo.
Olsnes
S
S
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002412:Cations / Q000378:metabolism; D002414:Cations, Monovalent; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D002794:Choline / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004167:Diphtheria Toxin / Q000494:pharmacology*; D005944:Glucosamine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011522:Protons; D012414:Rubidium Radioisotopes; D012964:Sodium / Q000378:metabolism; D012979:Sodium Radioisotopes; D013431:Sulfates / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology; D014709:Vero Cells
D002132:Calcium Radioisotopes; D002412:Cations; D002414:Cations, Monovalent; D002712:Chlorides; D004167:Diphtheria Toxin; D007473:Ion Channels; D011522:Protons; D012414:Rubidium Radioisotopes; D012979:Sodium Radioisotopes; D013431:Sulfates; D002104:Cadmium; D003035:Cobalt; D008345:Manganese; D012964:Sodium; D014700:Verapamil; D005944:Glucosamine; D002794:Choline; D011188:Potassium; D002118:Calcium