title: Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes.
abstract: The loss of intracellular potassium is a pivotal step in the induction of apoptosis but the mechanisms underlying this response are poorly understood. Here we report caspase-dependent stimulation of potassium channels by the Fas receptor in a human Jurkat T cell line. Receptor activation with Fas ligand for 30 min increased the amplitude of voltage-activated potassium currents 2-fold on average. This produces a sustained outward current, approximately 10 pA, at physiological membrane potentials during Fas ligand-induced apoptosis. Both basal and Fas ligand-induced currents were blocked completely by toxins that selectively inhibit Kv1.3 potassium channels. Kv1.3 stimulation required the expression of Fas-associated death domain protein and activation of caspase 8, but did not require activation of caspase 3 or protein synthesis. Furthermore, Kv1.3 stimulation by Fas ligand was prevented by chronic stimulation of protein kinase C with 20 nm phorbol 12-myristate 13-acetate during Fas ligand treatment, which also blocks apoptosis. Thus, Fas ligand increases Kv1.3 channel activity through the same canonical apoptotic signaling cascade that is required for potassium efflux, cell shrinkage, and apoptosis.
authors.affiliation: Membrane Signaling Group, Laboratory of Signal Transduction, Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Nina M
authors.initials: NM
authors.lastname: Storey
authors.forename: Mireia
authors.initials: M
authors.lastname: Gómez-Angelats
authors.forename: Carl D
authors.initials: CD
authors.lastname: Bortner
authors.forename: David L
authors.initials: DL
authors.lastname: Armstrong
authors.forename: John A
authors.initials: JA
authors.lastname: Cidlowski
mesh_terms: D017209:Apoptosis; D029681:Arabidopsis Proteins; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002469:Cell Separation; D004594:Electrophysiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007477:Ions; D019169:Jurkat Cells; D051664:Kv1.3 Potassium Channel; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011419:Propidium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D029681:Arabidopsis Proteins; D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007477:Ions; C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D008562:Membrane Glycoproteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D011419:Propidium; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; D011493:Protein Kinase C; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium