Channelpedia

PubMed 12807917


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kv1.3



Title: Stimulation of Kv1.3 potassium channels by death receptors during apoptosis in Jurkat T lymphocytes.

Authors: Nina M Storey, Mireia Gómez-Angelats, Carl D Bortner, David L Armstrong, John A Cidlowski

Journal, date & volume: J. Biol. Chem., 2003 Aug 29 , 278, 33319-26

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12807917


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.